Glaucoma implant with therapeutic agents

ABSTRACT

Devices and methods are provided for the treatment of glaucoma. An ocular implant is adapted such that aqueous humor flows controllably from the anterior chamber of the eye to Schlemm&#39;s canal, bypassing the trabecular meshwork. The implant may utilize one or more bioactive agents effective in treating glaucoma or other pathology.

CROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application is a continuation-in-part of U.S. patentapplication Ser. No. 10/395,633, filed Mar. 21, 2003, entitled “StentWith Drug Coating,” which is a continuation application of U.S. patentapplication Ser. No. 09/549,350, filed Apr. 14, 2000, entitled“Apparatus And Method For Treating Glaucoma.”

[0002] This application is also a continuation-in-part of U.S. patentapplication Ser. No. 10/634,213, filed Aug. 5, 2003, entitled “DevicesAnd Methods For Glaucoma Treatment,” which is a continuation-in-part ofU.S. patent application Ser. No. 10/118,578, filed Apr. 8, 2002,entitled “Glaucoma Stent And Methods Thereof For Glaucoma Treatment,”which claims the priority benefit of U.S. Provisional Application No.60/281,973, filed Apr. 7, 2001. The aforementioned U.S. patentapplication Ser. No. 10/634,213 also claims the priority benefits ofU.S. Provisional Application No. 60/401,166, filed Aug. 5, 2002, andU.S. Provisional Application No. 60/451,226, filed Feb. 28, 2003.

[0003] This application is also a continuation-in-part of U.S. patentapplication Ser. No. 10/046,137, filed Nov. 8, 2001, entitled“Drug-Releasing Trabecular Implant for Glaucoma Treatment,” which claimsthe priority benefit of U.S. Provisional Application No. 60/281,247,filed Apr. 3, 2001.

[0004] This application also claims the priority benefits of U.S.Provisional Patent Application No. 60/425,911, filed Nov. 12, 2002, andU.S. Provisional Patent Application No. 60/431,918, filed Dec. 9, 2002.

[0005] The entireties of all of the aforementioned priority documentsare hereby incorporated by reference.

BACKGROUND OF THE INVENTION

[0006] 1. Field of the Invention

[0007] The present application relates generally to medical devices andmethods for reducing the intraocular pressure in an animal eye and.,more particularly, to shunt-type stenting devices for permitting and/orenhancing aqueous outflow from the eye's anterior chamber towardexisting outflow pathways and associated methods thereof for thetreatment of glaucoma in general. Furthermore, the invention relates tothe delivery of bioactive agents to ocular tissue from an implant.

[0008] 2. Description of the Related Art

[0009] The human eye is a specialized sensory organ capable of lightreception and able to receive visual images. The trabecular meshworkserves as a drainage channel and is located in the anterior chamberangle formed between the iris and the cornea. The trabecular meshworkmaintains a balanced pressure in the anterior chamber of the eye byallowing aqueous humor to flow from the anterior chamber.

[0010] About two percent of people in the United States have glaucoma.Glaucoma is a group of eye diseases encompassing a broad spectrum ofclinical presentations, etiologies, and treatment modalities. Glaucomacauses pathological changes in the optic nerve, visible on the opticdisk, and it causes corresponding visual field loss, resulting inblindness if untreated. Lowering intraocular pressure is a majortreatment goal in all glaucomas.

[0011] In glaucomas associated with an elevation in eye pressure(intraocular hypertension), the source of resistance to outflow ofaqueous humor is mainly in the trabecular meshwork. The tissue of thetrabecular meshwork allows the aqueous humor (“aqueous”) to enterSchlemm's canal, which then empties into aqueous collector channels inthe posterior wall of Schlemm's canal and then into aqueous veins, whichform the episcleral venous system. Aqueous humor is a transparent liquidthat fills the region between the cornea, at the front of the eye, andthe lens. The aqueous humor is continuously secreted by the ciliary bodyaround the lens, so there is an essentially constant flow of aqueoushumor from the ciliary body to the eye's anterior chamber. The anteriorchamber pressure is determined by a balance between the production ofaqueous and its exit through the trabecular meshwork (major route) oruveal scleral outflow (minor route). The trabecular meshwork is locatedbetween the outer rim of the iris and the back of the cornea, in theanterior chamber angle. The portion of the trabecular meshwork adjacentto Schlemm's canal (the juxtacanilicular meshwork) causes most of theresistance to aqueous outflow.

[0012] Glaucoma is grossly classified into two categories: closed-angleglaucoma, also known as “angle closure” glaucoma, and open-angleglaucoma. Closed-angle glaucoma is caused by closure of the anteriorchamber angle by contact between the iris and the inner surface of thetrabecular meshwork. Closure of this anatomical angle prevents normaldrainage of aqueous humor from the anterior chamber of the eye.

[0013] Open-angle glaucoma is any glaucoma in which the angle of theanterior chamber remains open, but the exit of aqueous through thetrabecular meshwork is diminished. The exact cause for diminishedfiltration is unknown for most cases of open-angle glaucoma. Primaryopen-angle glaucoma is the most common of the glaucomas, and it is oftenasymptomatic in the early to moderately advanced stage. Patients maysuffer substantial, irreversible vision loss prior to diagnosis andtreatment. However, there are secondary open-angle glaucomas that mayinclude edema or swelling of the trabecular spaces (e.g., fromcorticosteroid use), abnormal pigment dispersion, or diseases such ashyperthyroidism that produce vascular congestion.

[0014] Current therapies for glaucoma are directed at decreasingintraocular pressure. Medical therapy includes topical ophthalmic dropsor oral medications that reduce the production or increase the outflowof aqueous. However, these drug therapies for glaucoma are sometimesassociated with significant side effects, such as headache, blurredvision, allergic reactions, death from cardiopulmonary complications,and potential interactions with other drugs. When drug therapy fails,surgical therapy is used. Surgical therapy for open-angle glaucomaconsists of laser trabeculoplasty, trabeculectomy, and implantation ofaqueous shunts after failure of trabeculectomy or if trabeculectomy isunlikely to succeed. Trabeculectomy is a major surgery that is widelyused and is augmented with topically applied anticancer drugs, such as5-flurouracil or mitomycin-C to decrease scarring and increase thelikelihood of surgical success.

[0015] Approximately 100,000 trabeculectomies are performed onMedicare-age patients per year in the United States. This number wouldlikely increase if the morbidity associated with trabeculectomy could bedecreased. The current morbidity associated with trabeculectomy consistsof failure (10-15%); infection (a life long risk of 2-5%); choroidalhemorrhage, a severe internal hemorrhage from low intraocular pressure,resulting in visual loss (1%); cataract formation; and hypotonymaculopathy (potentially reversible visual loss from low intraocularpressure).

[0016] For these reasons, surgeons have tried for decades to develop aworkable surgery for the trabecular meshwork.

[0017] The surgical techniques that have been tried and practiced aregoniotomy/trabeculotomy and other mechanical disruptions of thetrabecular meshwork, such as trabeculopuncture, goniophotoablation,laser trabecular ablation, and goniocurretage. These are all majoroperations and are briefly described below.

[0018] Goniotomy/Trabeculotomy: Goniotomy and trabeculotomy are simpleand directed techniques of microsurgical dissection with mechanicaldisruption of the trabecular meshwork. These initially had earlyfavorable responses in the treatment of open-angle glaucoma. However,long-term review of surgical results showed only limited success inadults. In retrospect, these procedures probably failed due to cellularrepair and fibrosis mechanisms and a process of “filling in.” Filling inis a detrimental effect of collapsing and closing in of the openingcreated in the trabecular meshwork. Once the openings close, thepressure builds back up and the surgery fails.

[0019] Trabeculopuncture: Q-switched Neodymium (Nd) YAG lasers also havebeen investigated as an optically invasive technique for creatingfull-thickness holes in trabecular meshwork. However, the relativelysmall hole created by this trabeculopuncture technique exhibits afilling-in effect and fails.

[0020] Goniophotoablation/Laser Trabecular Ablation: Goniophotoablationis disclosed by Berlin in U.S. Pat. No. 4,846,172 and involves the useof an excimer laser to treat glaucoma by ablating the trabecularmeshwork. This was demonstrated not to succeed by clinical trial. Hillet al. disclosed the use of an Erbium:YAG laser to create full-thicknessholes through trabecular meshwork (Hill et al., Lasers in Surgery andMedicine 11:341-346, 1991). This technique was investigated in a primatemodel and a limited human clinical trial at the University ofCalifornia, Irvine. Although morbidity was zero in both trials, successrates did not warrant further human trials. Failure was again fromfilling in of surgically created defects in the trabecular meshwork byrepair mechanisms. Neither of these is a viable surgical technique forthe treatment of glaucoma.

[0021] Goniocurretage: This is an ab interno (from the inside),mechanically disruptive technique that uses an instrument similar to acyclodialysis spatula with a microcurrette at the tip. Initial resultswere similar to trabeculotomy: it failed due to repair mechanisms and aprocess of filling in.

[0022] Although trabeculectomy is the most commonly performed filteringsurgery, viscocanalostomy (VC) and non-penetrating trabeculectomy (NPT)are two new variations of filtering surgery. These are ab externo (fromthe outside), major ocular procedures in which Schlemm's canal issurgically exposed by making a large and very deep scleral flap. In theVC procedure, Schlemm's canal is cannulated and viscoelastic substanceinjected (which dilates Schlemm's canal and the aqueous collectorchannels). In the NPT procedure, the inner wall of Schlemm's canal isstripped off after surgically exposing the canal.

[0023] Trabeculectomy, VC, and NPT involve the formation of an openingor hole under the conjunctiva and scleral flap into the anteriorchamber, such that aqueous humor is drained onto the surface of the eyeor into the tissues located within the lateral wall of the eye. Thesesurgical operations are major procedures with significant ocularmorbidity. Where trabeculectomy, VC, and NPT were thought to have a lowchance for success in particular cases, a number of implantable drainagedevices have been used to ensure that the desired filtration and outflowof aqueous humor through the surgical opening will continue. The risk ofplacing a glaucoma drainage device also includes hemorrhage, infection,and diplopia (double vision).

[0024] All of the above surgeries and variations thereof have numerousdisadvantages and moderate success rates. They involve substantialtrauma to the eye and require great surgical skill in creating a holethrough the full thickness of the sclera into the subconjunctival space.The procedures are generally performed in an operating room and have aprolonged recovery time for vision.

[0025] The complications of existing filtration surgery have promptedophthalmic surgeons to find other approaches to lowering intraocularpressure or treating tissue of trabecular meshwork.

[0026] The trabecular meshwork and juxtacanilicular tissue togetherprovide the majority of resistance to the outflow of aqueous and, assuch, are logical targets for tissue stimulation/rejuvenating orshunting in the treatment of open-angle glaucoma. In addition, minimalamounts of tissue are displaced and functions of the existingphysiologic outflow pathways are restored.

[0027] As reported in Arch. Ophthalm. (2000) 118:412, glaucoma remains aleading cause of blindness, and filtration surgery remains an effective,important option in controlling the disease. However, modifying existingfiltering surgery techniques in any profound way to increase theireffectiveness appears to have reached a dead end. The article furtherstates that the time has come to search for new surgical approaches thatmay provide better and safer care for patients with glaucoma.

[0028] Examples of implantable shunts and surgical methods formaintaining an opening for the release of aqueous from the anteriorchamber of the eye to the sclera or space beneath the conjunctiva havebeen disclosed in, for example, Hsia et al., U.S. Pat. No. 6,059,772 andBaerveldt, U.S. Pat. No. 6,050,970.

[0029] Examples of implantable shunts or devices for maintaining anopening for the release of aqueous humor from the anterior chamber ofthe eye to the sclera or space underneath conjunctiva have beendisclosed in U.S. Pat. No. 6,007,511 (Prywes), U.S. Pat. No. 6,007,510(Nigam), U.S. Pat. No. 5,893,837 (Eagles et al.), U.S. Pat. No.5,882,327 (Jacob), U.S. Pat. No. 5,879,319 (Pynson et al.), U.S. Pat.No. 5,807,302 (Wandel), U.S. Pat. No. 5,752,928 (de Roulhac et al.),U.S. Pat. No. 5,743,868 (Brown et al.), U.S. Pat. No. 5,704,907(Nordquist et al.), U.S. Pat. No. 5,626,559 (Solomon), U.S. Pat. No.5,626,558 (Suson), U.S. Pat. No. 5,601,094 (Reiss), RE. 35,390 (Smith),U.S. Pat. No. 5,558,630 (Fisher), U.S. Pat. No. 5,558,629 (Baerveldt etal.), U.S. Pat. No. 5,520,631 (Nordquist et al.), U.S. Pat. No.5,476,445 (Baerveldt et al.), U.S. Pat. No. 5,454,796 (Krupin), U.S.Pat. No. 5,433,701 (Rubinstein), U.S. Pat. No. 5,397,300 (Baerveldt etal.), U.S. Pat. No. 5,372,577 (Ungerleider), U.S. Pat. No. 5,370,607(Memmen), U.S. Pat. No. 5,338,291 (Speckman et al.), U.S. Pat. No.5,300,020 (L'Esperance, Jr.), U.S. Pat. No. 5,178,604 (Baerveldt etal.), U.S. Pat. No. 5,171,213 (Price, Jr.), U.S. Pat. No. 5,041,081(Odrich), U.S. Pat. No. 4,968,296 (Ritch et al.), U.S. Pat. No.4,936,825 (Ungerleider), U.S. Pat. No. 4,886,488 (White), U.S. Pat. No.4,750,901 (Molteno), U.S. Pat. No. 4,634,418 (Binder), U.S. Pat. No.4,604,087 (Joseph), U.S. Pat. No. 4,554,918 (White), U.S. Pat. No.4,521,210 (Wong), U.S. Pat. No. 4,428,746 (Mendez), U.S. Pat. No.4,402,681 (Haas et al.), U.S. Pat. No. 4,175,563 (Arenberg et al.), andU.S. Pat. No. 4,037,604 (Newkirk).

[0030] All of the above embodiments and variations thereof have numerousdisadvantages and moderate success rates. They involve substantialtrauma to the eye and require great surgical skill in creating a holethrough the full thickness of the sclera into the subconjunctival space.The procedures are generally performed in an operating room and involvea prolonged recovery time for vision. The complications of existingfiltration surgery have prompted ophthalmic surgeons to find otherapproaches to lowering intraocular pressure.

[0031] Because the trabecular meshwork and juxtacanilicular tissuetogether provide the majority of resistance to the outflow of aqueous,they are logical targets for surgical removal in the treatment ofopen-angle glaucoma. In addition, minimal amounts of tissue need bealtered and existing physiologic outflow pathways can be utilized.

SUMMARY OF THE INVENTION

[0032] What is needed, therefore, is an extended, site-specifictreatment method for glaucoma that is faster, safer, and less expensivethan currently available modalities. There is a great clinical need foran improved method of treating glaucoma that is faster, safer, and lessexpensive than currently available drug or surgical modalities. Themethods disclosed herein include ab interno and ab externo proceduresthat involve non-flap operations. The method herein may further compriseusing an innovative stenting device.

[0033] In some preferred embodiments, the seton has an inlet portionconfigured to extend through a portion of the trabecular meshwork of aneye, and an outlet portion configured to extend into Schlemm's canal ofthe eye, wherein the inlet portion is disposed at an angle relative tothe outlet portion. In some embodiments, the outlet portion has a lumenwith an oval cross-section having a long axis.

[0034] The outlet portion in certain embodiments has a longitudinalaxis, such that the long axis of the oval cross-section and thelongitudinal axis of the outlet portion define a plane, the inletportion having a longitudinal axis that lies outside the plane at anangle θ (theta) thereto.

[0035] In some preferred arrangements, the seton comprises an inletportion, configured to extend through a portion of the trabecularmeshwork; an outlet portion, configured to extend into Schlemm's canal;and at least one protrusion on the outlet portion, configured to exerttraction against an inner surface of Schlemm's canal. This protrusioncan comprise at least one barb or ridge.

[0036] Some preferred embodiments comprise an inlet portion configuredto extend through a portion of the trabecular meshwork, an outletportion configured to extend into Schlemm's canal, and a one-way valvewithin the inlet and/or outlet portions.

[0037] A method for delivering a seton within an eye is disclosed,comprising providing an elongate guide member, advancing a distal end ofthe guide member through at least a portion of the trabecular meshworkof the eye, advancing the seton along the guide member toward the distalend, and positioning the seton to conduct aqueous humor between theanterior chamber of the eye and Schlemm's canal.

[0038] In certain embodiments, the advancing of the guide membercomprises advancing it from the anterior chamber into the trabecularmeshwork. In further embodiments, the positioning comprises positioningan end of the seton within Schlemm's canal adjacent to an aqueouscollection channel.

[0039] Certain preferred embodiments include an apparatus for deliveringa seton to the anterior chamber of an eye comprising an elongate tubehaving a lumen, an outer surface, and a distal end; a removable,elongate guide member within the lumen, configured to permit the setonto be advanced and to be positioned in the trabecular meshwork of theeye. This apparatus can further comprise a cutting member positioned atthe distal end of the tube. The cutting member can be selected from thegroup consisting of a knife, a laser probe, a pointed guide member, asharpened distal end of said tube, and an ultrasonic cutter. Theapparatus can also further comprise an opening in the outer surface ofthe tube, configured to allow fluid infusion into the eye.

[0040] In further preferred embodiments, an apparatus for delivering aseton in an eye, comprises an elongate member adapted for insertion intoan anterior chamber of the eye, the elongate member having a distal endportion configured to retain the seton therein, the distal end portioncomprising a cutting member configured to form an opening in thetrabecular meshwork of the eye for receipt of the seton, such that oneend of the seton is in Schlemm's canal. The elongate member can furthercomprise a lumen that conducts fluid toward said distal end portion.

[0041] The preferred embodiment provides further surgical treatment ofglaucoma (trabecular bypass surgery) at the level of trabecular meshworkand restores existing physiological outflow pathways. An implantbypasses diseased trabecular meshwork at the level of trabecularmeshwork and which restores existing physiological outflow pathways. Theimplant has an inlet end, an outlet end and a lumen therebetween. Theinlet is positioned in the anterior chamber at the level of the internaltrabecular meshwork and the outlet end is positioned at about theexterior surface of the diseased trabecular meshwork and/or into fluidcollection channels of the existing outflow pathways.

[0042] In accordance with a preferred method, trabecular bypass surgerycreates an opening or a hole through the diseased trabecular meshworkthrough minor microsurgery. To prevent “filling in” of the hole, abiocompatible elongated implant is placed within the hole as a seton,which may include, for example, a solid rod or hollow tube. In oneexemplary embodiment, the seton implant may be positioned across thediseased trabecular meshwork alone and it does not extend into the eyewall or sclera. In another embodiment, the inlet end of the implant isexposed to the anterior chamber of the eye while the outlet end ispositioned at the exterior surface of the trabecular meshwork. Inanother exemplary embodiment, the outlet end is positioned at and overthe exterior surface of the trabecular meshwork and into the fluidcollection channels of the existing outflow pathways. In still anotherembodiment, the outlet end is positioned in the Schlemm's canal. In analternative embodiment, the outlet end enters into fluid collectionchannels up to the level of the aqueous veins with the seton inserted ina retrograde or antegrade fashion.

[0043] According to the preferred embodiment, the seton implant is madeof biocompatible material, which is either hollow to allow the flow ofaqueous humor or solid biocompatible material that imbibes aqueous. Thematerial for the seton may be selected from the group consisting ofporous material, semi-rigid material, soft material, hydrophilicmaterial, hydrophobic material, hydrogel, elastic material, and thelike.

[0044] In further accordance with the preferred embodiment, the setonimplant may be rigid or it may be made of relatively soft material andis somewhat curved at its distal section to fit into the existingphysiological outflow pathways, such as Schlemm's canal. The distalsection inside the outflow pathways may have an oval shape to stabilizethe seton in place without undue suturing. Stabilization or retention ofthe seton may be further strengthened by a taper end and/or by at leastone ridge or rib on the exterior surface of the distal section of theseton, or other surface alterations designed to retain the seton.

[0045] In one embodiment, the seton may include a micropump, one-wayvalve, or semi-permeable membrane if reflux of red blood cells or serumprotein becomes a clinical problem. It may also be useful to use abiocompatible material that hydrates and expands after implantation sothat the seton is locked into position around the trabecular meshworkopening or around the distal section of the seton.

[0046] One of the advantages of trabecular bypass surgery, as disclosedherein, and the use of a seton implant to bypass diseased trabecularmeshwork at the level of trabecular meshwork and thereby use existingoutflow pathways is that the treatment of glaucoma is substantiallysimpler than in existing therapies. A further advantage of the inventionis the utilization of simple microsurgery that may be performed on anoutpatient basis with rapid visual recovery and greatly decreasedmorbidity. Finally, a distinctly different approach is used than isfound in existing implants. Physiological outflow mechanisms are used orre-established by the implant of the present invention, incontradistinction with previously disclosed methodologies.

[0047] A device and method are provided for improved treatment ofintraocular pressure due to glaucoma. A trabecular shunting and stentingdevice is adapted for implantation within a trabecular meshwork of aneye such that aqueous humor flows controllably from an anterior chamberof the eye to Schlemm's canal, bypassing the trabecular meshwork. Thetrabecular stenting device comprises a quantity of bioactive agentseffective in treating glaucoma, which are controllably released from thedevice into cells of the trabecular meshwork and/or Schlemm's canal.Depending upon the specific treatment contemplated, bioactive agents maybe utilized in conjunction with the trabecular stenting device such thataqueous flow either increases or decreases as desired. Placement of thetrabecular stenting device within the eye and incorporation, andeventual release, of a proven bioactive agents glaucoma therapy willreduce, inhibit or slow the effects of glaucoma.

[0048] One aspect of the invention provides a trabecular stenting devicethat is implantable within an eye. The device comprises an inlet sectioncontaining at least one lumen, an outlet section having at least oneoutlet end. In one embodiment, there provides a flow-restricting memberwithin the lumen that is configured to prevent at least one component ofblood from passing through the flow-restricting member. In anotherembodiment, the device further comprises a middle section having atleast one lumen. The middle section is fixedly attached between theinlet section and the outlet section and the lumen is in fluidcommunication with the lumens of the inlet and outlet sections. Thedevice is configured to permit fluid entering the lumens of the inletsection, the middle section, and the outlet section, and then exit theoutlet section through the at least one outlet end.

[0049] Another aspect of the invention provides a method of treatingglaucoma. The method comprises providing at least one bioactive agent orsubstance incorporated into a trabecular stenting device, implanting thetrabecular stenting device within a trabecular meshwork of an eye suchthat a first end of the trabecular stent is positioned in an anteriorchamber of the eye while a second end is positioned in a Schlemm'scanal, and allowing the stenting device to release a quantity of thebioactive agent into the eye. The first and second ends of thetrabecular stenting device establish a fluid communication between theanterior chamber and the Schlemm's canal.

[0050] In another aspect of the invention, the bioactive agent comprisesgenes, growth factors, TGF-beta, scar inhibitors, and the like.

[0051] Still another aspect of the invention provides a method ofregulating intraocular pressure within an eye. The method comprises:providing at least one bioactive agent incorporated into a trabecularstenting device; implanting the trabecular stenting device within atrabecular meshwork of an eye such that a first end of the trabecularstent is positioned in an anterior chamber of the eye while a second endis positioned in a Schlemm's canal, wherein the first and second ends ofthe trabecular stenting device establish a fluid communication betweenthe anterior chamber and the Schlemm's canal; and allowing the stentingdevice to release a quantity of said bioactive agent into the eye.

[0052] Another aspect of the invention provides an apparatus forimplanting a trabecular shunting/stenting device within an eye. Theapparatus comprises a syringe portion and a cannula portion that hasproximal and distal ends. The proximal end of the cannula portion isattached to the syringe portion. The cannula portion further comprises afirst lumen and at least one irrigating hole disposed between theproximal and distal ends of the cannula portion. The irrigating hole isin fluid communication with the lumen. The apparatus further includes aholder comprising a second lumen for holding the trabecular stentingdevice. A distal end of the second lumen opens to the distal end of thecannula portion, and a proximal end of the second lumen is separatedfrom the first lumen of the cannula portion. The holder holds thetrabecular stenting device during implantation of the device within theeye, and the holder releases the trabecular stenting device when apractitioner activates deployment of the device.

[0053] Another aspect of the invention provides a method of implanting atrabecular stenting device within an eye. The method comprises creatinga first incision in a cornea on a first side of the eye, wherein thefirst incision passes through the cornea into an anterior chamber of theeye. The method further comprises passing an incising device through thefirst incision and moving a distal end of the incising device across theanterior chamber to a trabecular meshwork residing on a second side ofthe eye, and using the incising device to create a second incision. Thesecond incision is in the trabecular meshwork, passing from the anteriorchamber through the trabecular meshwork into a Schlemm's canal. Themethod further comprises inserting the trabecular shunting/stentingdevice into a distal space of a delivery applicator. The method furthercomprises advancing the cannula portion having the trabecular stentingdevice through the first incision, across the anterior chamber and intothe second incision, wherein an outlet section of the trabecularstenting device is implanted into Schlemm's canal while an inlet sectionof the trabecular stenting device remains in fluid communication withthe anterior chamber. The method still further comprises releasing thetrabecular stenting device from the holder of the delivery applicator.

[0054] The trabecular meshwork and juxtacanilicular tissue togetherprovide the majority of resistance to the outflow of aqueous and, assuch, are logical targets for the treatment of glaucoma. Variousembodiments of glaucoma devices and methods are disclosed herein fortreating glaucoma by an ab interno procedure or an ab externo procedure,with respect to trabecular meshwork. The “ab interno” procedure isherein intended to mean any procedure that creates an opening from theanterior chamber through trabecular meshwork outwardly toward Schlemm'scanal or toward scleral/cornea wall. This ab interno procedure may beinitiated through the scleral wall or cornea wall into the anteriorchamber as a first step. The “ab externo” procedure is herein intendedto mean any procedure that creates an opening on the scleral wallthrough trabecular meshwork inwardly toward the anterior chamber. Inmost “ab externo” procedures disclosed herein, an instrument is passedthrough or contacts Schlemm's canal before entering trabecular meshworkand approaching the anterior chamber. The trabecular meshwork cangenerally be said to be bordered on one side by the anterior chamber andon the other side by Schlemm's canal.

[0055] Glaucoma surgical morbidity would greatly decrease if one were tobypass the focal resistance to outflow of aqueous only at the point ofresistance, and to utilize remaining, healthy aqueous outflowmechanisms. This is in part because episcleral aqueous humor exerts abackpressure that prevents intraocular pressure from falling too low,and one could thereby avoid hypotony. Thus, such a surgery wouldvirtually eliminate the risk of hypotony-related maculopathy andchoroidal hemorrhage. Furthermore, visual recovery would be very rapid,and the risk of infection would be very small, reflecting a reduction inincidence from 2-5% to about 0.05%.

[0056] Copending U.S. application Ser. No. 09/549,350, filed Apr. 14,2000, entitled APPARATUS AND METHOD FOR TREATING GLAUCOMA, and copendingU.S. application Ser. No. 09/704,276, filed Nov. 1, 2000, entitledGLAUCOMA TREATMENT DEVICE, disclose devices and methods of placing atrabecular shunt ab interno, i.e., from inside the anterior chamberthrough the trabecular meshwork, into Schlemm's canal. The entirecontents of each one of these copending patent applications are herebyincorporated by reference herein. This application encompasses both abinterno and ab externo glaucoma shunts or stents and methods thereof.

[0057] One technique performed in accordance with certain aspects hereincan be referred to generally as “trabecular bypass surgery.” Advantagesof this type of surgery include lowering intraocular pressure in amanner that is simple, effective, disease site-specific, and canpotentially be performed on an outpatient basis.

[0058] Generally, trabecular bypass surgery (TBS) creates an opening, aslit, or a hole through trabecular meshwork with minor microsurgery. TBShas the advantage of a much lower risk of choroidal hemorrhage andinfection than prior techniques, and it uses existing physiologicoutflow mechanisms. In some aspects, this surgery can potentially beperformed under topical or local anesthesia on an outpatient basis withrapid visual recovery. To prevent “filling in” of the hole, abiocompatible elongated hollow device is placed within the hole andserves as a stent. U.S. patent application Ser. No. 09/549,350, filedApr. 14, 2000 and the corresponding WO PCT US 01/07398 filed Mar. 8,2001, the entire contents of which are hereby incorporated by referenceherein, disclose trabecular bypass surgery in details.

[0059] As described in U.S. Patent Application. No. 09/549,350, filedApr. 14, 2000, and U.S. application Ser. No. 09/704,276, filed Nov. 1,2000, a trabecular shunt or stent for transporting aqueous humor isprovided. The trabecular stent includes a hollow, elongate tubularelement, having an inlet section and an outlet section. The outletsection may optionally include two segments or elements, adapted to bepositioned and stabilized inside Schlemm's canal. In one embodiment, thedevice appears as a “T” or an “L” shaped device.

[0060] In accordance with one aspect of at least one of the inventionsdisclosed herein, a delivery apparatus (or “applicator”) is used forplacing a trabecular stent through a trabecular meshwork of an eye.Certain embodiments of such a delivery apparatus are disclosed incopending U.S. application Ser. No. 10/101,548, filed Mar. 18, 2002,entitled APPLICATOR AND METHODS FOR PLACING A TRABECULAR SHUNT FORGLAUCOMA TREATMENT, and U.S. Provisional Application No. 60/276,609,filed Mar. 16, 2001, entitled APPLICATOR AND METHODS FOR PLACING ATRABECULAR SHUNT FOR GLAUCOMA TREATMENT, the entire contents of each oneof which are hereby incorporated by reference herein.

[0061] The stent has an inlet section and an outlet section. Thedelivery apparatus includes a handpiece, an elongate tip, a holder andan actuator. The handpiece has a distal end and a proximal end. Theelongate tip is connected to the distal end of the handpiece. Theelongate tip has a distal portion and is configured to be placed througha corneal incision and into an anterior chamber of the eye. The holderis attached to the distal portion of the elongate tip. The holder isconfigured to hold and release the inlet section of the trabecularstent. The actuator is on the handpiece and actuates the holder torelease the inlet section of the trabecular stent from the holder. Whenthe trabecular stent is deployed from the delivery apparatus into theeye, the outlet section is positioned in substantially oppositedirections inside Schlemm's canal. In one embodiment, a deploymentmechanism within the delivery apparatus includes a push-pull typeplunger.

[0062] Some aspects of at least one of the inventions disclosed hereinrelate to devices for reducing intraocular pressure by providing outflowof aqueous from an anterior chamber of an eye. The device generallycomprises an elongated tubular member and cutting means. The tubularmember is adapted for extending through a trabecular meshwork of theeye. The tubular member generally comprises a lumen having an inlet portand at least one outlet port for providing a flow pathway. The cuttingmeans is mechanically connected to or is an integral part of the tubularmember for creating an incision in the trabecular meshwork for receivingat least a portion of the tubular member.

[0063] In one embodiment, a self-trephining glaucoma stent is providedfor reducing and/or balancing intraocular pressure in an eye. The stentgenerally comprises a snorkel and a curved blade. The snorkel generallycomprises an upper seat for stabilizing said stent within the eye, ashank and a lumen. The shank is mechanically connected to the seat andis adapted for extending through a trabecular meshwork of the eye. Thelumen extends through the snorkel and has at least one inlet flow portand at least one outlet flow port. The blade is mechanically connectedto the snorkel. The blade generally comprises a cutting tip proximate adistal-most point of the blade for making an incision in the trabecularmeshwork for receiving the shank.

[0064] Some aspects of at least one of the inventions disclosed hereinrelate to methods of implanting a trabecular stent device in an eye. Inone embodiment, the device has a snorkel mechanically connected to ablade. The blade is advanced through a trabecular meshwork of the eye tocut the trabecular meshwork and form an incision therein. At least aportion of the snorkel is inserted in the incision to implant the devicein the eye.

[0065] Some aspects provide a self-trephining glaucoma stent and methodsthereof, which advantageously allow for a “one-step” procedure in whichthe incision and placement of the stent are accomplished by a singledevice and operation. This desirably allows for a faster, safer, andless expensive surgical procedure. In any of the embodiments, fiducialmarkings, indicia, or the like and/or positioning of the stent device ina preloaded applicator may be used for proper orientation and alignmentof the device during implantation.

[0066] Among the advantages of trabecular bypass surgery is itssimplicity. The microsurgery may potentially be performed on anoutpatient basis with rapid visual recovery and greatly decreasedmorbidity. There is a lower risk of infection and choroidal hemorrhage,and there is a faster recovery, than with previous techniques.

[0067] Some aspects of at least one of the inventions disclosed hereinrelate to a medical device system for treating glaucoma of an eyecomprising using OCT (optical coherence tomography) as an imaging andlocating system for trabecular stent placement. In one embodiment, theprocedure would first be set up with triangulation or some means toreliably establish the implant location in x, y, and z coordinates byusing OCT within a few microns, most preferably in a non-invasive,non-contact manner. Having acquired the target space or location, thetrabecular stent device would then be injected into place either via anab interno procedure or an ab externo procedure. An article by Hoeraufet al. (Greafe's Arch Clin Exp Ophthalmol 2000; 238:8-18 published bySpringer-Verlag), entire contents of which are incorporated herein byreference, discloses a slit-lamp adapted optical coherence tomography ofthe anterior segment.

[0068] Some aspects of at least one of the inventions disclosed hereinrelate to a ‘foldable’ stent wherein the size of the stent is reduced inorder to place it through a yet smaller ocular entrance wound, as smallas half or less than the size of the unfolded stent. The smallest sizewound is important to aid in recovery, to prevent complications, and tominimize the preparation and extent of the surgical environment. Inanother embodiment, the device is positioned through the trabecularmeshwork in an ab externo or ab interno procedure. Reliablevisualization (OCT, UBM, gonioscope, electromagnetic or other means) isa key enabler for micro precision surgery such as a trabecular bypasssurgery using a microstent.

[0069] Some aspects of at least one of the inventions disclosed hereinrelate to a medical device system with trephining capability, wherein acutting mechanism is on or as part of the applicator for purposes ofmaking the hole in trabecular meshwork for stent insertion. In oneaspect, a cutting tip may protrude through the lumen of the stent. Inanother, the tip extends down the side of the snorkel without enteringthe lumen. In still another, the tip either passes through the lumen ordown the side and further extends to the tip of the stent that is theleading edge during insertion. In one embodiment, the cutting tip can bedesigned to retract after making the incision but before insertion ofthe stent into Schlemm's canal if it interferes with the insertionoperation. It could also be retracted after insertion of the stent intoSchlemm's canal.

[0070] Some aspects of at least one of the inventions disclosed hereinprovide an implant for treating glaucoma, the implant having alongitudinal implant axis, and comprising an outflow portion throughwhich a portion of the longitudinal implant axis passes, the outflowportion shaped and sized to be (a) introduced into Schlemm's canal withthe portion of the longitudinal implant axis at an angle to Schlemm'scanal; and (b) received with Schlemm's canal regardless of therotational orientation of the outflow portion about the portion of thelongitudinal implant axis during the introduction; and an inflow portionin fluid communication with the outflow portion, the inflow portionconfigured to permit communication of fluid from the anterior chamber ofthe eye to the outflow portion.

[0071] Some aspects of at least one of the inventions disclosed hereinprovide an implant for treating glaucoma, comprising: an outflowportion, sized and shaped to be received within Schlemm's canal, theoutflow portion comprising: an outflow portion base having an outflowopening and at least one standoff member disposed to space the outflowopening from a wall of Schlemm's canal, such that the opening isunobstructed by the canal wall.

[0072] Some aspects of at least one of the inventions disclosed hereinprovide an implant for treating glaucoma, the implant having alongitudinal implant axis and comprising: a first portion at a first endof the longitudinal implant axis, the first portion sized and configuredto reside in Schlemm's canal, such that the first portion has a maximumdimension along a longitudinal axis of Schlemm's canal that is notsubstantially greater than a dimension of the first portion that runsperpendicular to both the longitudinal axis of Schlemm's canal and tothe longitudinal implant axis; and a second portion at a second end ofthe longitudinal implant axis, the second portion configured to providefluid communication between the anterior chamber and the first portion.

[0073] Some aspects of at least one of the inventions disclosed hereinprovide an implant for treating glaucoma, comprising: an outflowportion, sized and shaped to be received within Schlemm's canal; aninflow portion in fluid communication with the outflow portion, theinflow portion configured to be disposed in the anterior chamber of theeye; and a central portion extending between the inflow and outflowportions; the outflow portion having a diameter that is no more thanthree times the diameter of the central portion.

[0074] In accordance with one embodiment of at least one of theinventions disclosed herein, an implant for treating glaucoma isprovided. The implant includes a longitudinal implant axis, andcomprises an outflow portion through which said longitudinal implantaxis passes. The outflow portion is shaped and sized to be introducedinto Schlemm's canal with the portion of the longitudinal implant axisat an angle to Schlemm's canal. The outflow portion is also shaped andsized to be received within Schlemm's canal regardless of a rotationalorientation of the outflow portion about said longitudinal implant axisduring said introduction. The implant also comprises an inflow portionconfigured to permit communication of fluid from the anterior chamber ofthe eye to the outflow portion.

[0075] In accordance with another embodiment of at least one of theinventions disclosed herein, an implant for treating glaucoma isprovided. The implant comprises an outflow portion, sized and shaped tobe received within Schlemm's canal. The outflow portion comprises anoutflow portion base having an outflow opening and at least one standoffmember disposed to space said outflow opening from a wall of Schlemm'scanal, such that said outflow opening is unobstructed by said canalwall.

[0076] In accordance with a further embodiment of at least one of theinventions disclosed herein, an implant for treating glaucoma isprovided. The implant includes a longitudinal implant axis and comprisesa first portion at a first end of said longitudinal implant axis. Thefirst portion is sized and configured to reside in Schlemm's canal, suchthat said first portion has a maximum dimension along a longitudinalaxis of Schlemm's canal that is not substantially greater than adimension of the first portion that runs perpendicular to both saidlongitudinal axis of Schlemm's canal and to said longitudinal implantaxis. A second portion at a second end of said longitudinal implant axisis configured to provide fluid communication between the anteriorchamber and said first portion.

[0077] In accordance with yet another embodiment of at least one of theinventions disclosed herein, an implant for treating glaucoma comprisesan outflow portion, sized and shaped to be received within Schlemm'scanal. An inflow portion is in fluid communication with said outflowportion, the inflow portion configured to be disposed in the anteriorchamber of the eye. A central portion extending between the inflow andoutflow portions. The outflow portion having a diameter that is no morethan three times the diameter of the central portion.

[0078] In accordance with yet another embodiment of at least one of theinventions disclosed herein, an instrument for delivering implants fortreating an ophthalmic condition is provided. The instrument comprisesan elongate body sized to be introduced into an eye through an incisionin the eye. A plurality of implants is positioned in the elongate body.The elongate body further comprises an actuator that serially dispensesthe implants from the elongate body for implanting in eye tissue.

[0079] In accordance with another embodiment of at least one of theinventions disclosed herein, a method of implanting a plurality ofimplants for treating glaucoma is provided. The method includesinserting an instrument into an eye through an incision, utilizing theinstrument to deliver a first implant through a wall of Schlemm's canalat a first location, and utilizing the instrument to deliver a secondimplant through a wall of Schlemm's canal at a second location, withoutremoving the instrument from the eye between the deliveries of saidimplants.

[0080] In accordance with yet another embodiment of at least one of theinventions disclosed herein, a method of implanting a plurality ofimplants for treating glaucoma is provided. The method includesinserting an instrument into an eye through an incision, utilizing theinstrument to deliver a first implant through a wall of Schlemm's canalat a first location, and utilizing the instrument to deliver a secondimplant through a wall of Schlemm's canal at a second location, whereinthe locations are determined from morphological data on collectorchannel locations.

[0081] In accordance with yet another embodiment of at least one of theinventions disclosed herein, a method of implanting a plurality ofimplants for treating glaucoma is provided. The method comprisesinserting an instrument into an eye through an incision, utilizing theinstrument to deliver a first implant through a wall of Schlemm's canalat a first location, and utilizing said instrument to deliver a secondimplant through a wall of Schlemm's canal at a second location. Thelocations are determined by imaging collector channel locations.

[0082] In accordance with a further embodiment of at least one of theinventions disclosed herein, a method of implanting a plurality ofimplants for treating glaucoma is provided. The method comprisesinserting an instrument into an eye through an incision, utilizing theinstrument to deliver a first implant through a wall of Schlemm's canalat a first location, and utilizing said instrument to deliver a secondimplant through a wall of Schlemm's canal at a second location. Thelocations are angularly spaced along Schlemm's canal by at least 20degrees.

[0083] In accordance with yet another embodiment of at least one of theinventions disclosed herein, a method of implanting a plurality ofimplants for treating glaucoma is provided. The method comprisesinserting an instrument into an eye through an incision, utilizing theinstrument to deliver a first implant through a wall of Schlemm's canalat a first location, utilizing the instrument to deliver a secondimplant through a wall of Schlemm's canal at a second location. Thefirst and second locations are substantially at collector channels.

[0084] In accordance with another embodiment of at least one of theinventions disclosed herein, a method of implanting a plurality ofimplants for treating glaucoma is provided. The method comprisesinserting an instrument into an eye through an incision, utilizing theinstrument to deliver a first implant through a wall of Schlemm's canalat a first location, and utilizing said instrument to deliver a secondimplant through a wall of Schlemm's canal at a second location. Theimplants have different flow characteristics.

[0085] In accordance with yet another embodiment of at least one of theinventions disclosed herein, a method of implanting a plurality ofimplants for treating glaucoma is provided. The method comprisesinserting an instrument into an eye through an incision, utilizing theinstrument to deliver a first implant into the posterior segment of theeye, and utilizing the instrument to deliver a second implant into theposterior segment of the eye at a second location. The instrument is notremoved from the eye between said deliveries of the implants.

[0086] In accordance with a further embodiment of at least one of theinventions disclosed herein, a method of implanting a plurality ofimplants for treating glaucoma is provided. The method comprisesserially dispensing a plurality of preloaded implants from an instrumentinto eye tissue at a respective plurality of locations within the eye.

[0087] For purposes of summarizing, certain aspects, advantages andnovel features of the inventions disclosed herein have been describedherein above. Of course, it is to be understood that not necessarily allsuch advantages may be achieved in accordance with any particularembodiment. Thus, the inventions may be embodied or carried out in amanner that achieves or optimizes one advantage or group of advantagesas taught or suggested herein without necessarily achieving otheradvantages as may be taught or suggested herein.

[0088] Some embodiments include an implant for treating glaucoma,comprising a body comprising material that includes a drug, the bodyhaving an inlet portion and an outlet portion, the inlet portionconfigured to transport fluid from the anterior chamber of an eye to theoutlet portion when the outlet portion is disposed in Schlemm's canal ofthe eye, the outlet portion having an outflow opening.

[0089] In some embodiments, the body is coated with the drug. In someembodiments, the drug comprises heparin.

[0090] Some embodiments include an implant for treating glaucoma,comprising a body having a bioactive agent in or on the body, the bodyhaving an inlet portion and an outlet portion, the inlet portionconfigured to transmit fluid from the anterior chamber to the outletportion when the outlet portion is disposed in Schlemm's canal, theoutlet portion having an outflow opening.

[0091] In some embodiments, the bioactive agent comprises TGF-beta, agene, an anti-inflammatory drug, and/or an intraocular pressure-loweringdrug.

[0092] In some embodiments, the bioactive agent comprises a growthfactor and/or an antiproliferative agent.

[0093] In some embodiments, the bioactive agent is loaded onto a surfaceof the outlet section.

[0094] Some embodiments further comprise a biodegradable material in oron the implant. In some embodiments, the biodegradable material isselected from the group consisting of poly(lactic acid),polyethylene-vinyl acetate, poly(lactic-co-glycolic acid),poly(D,L-lactide), poly(D,L-lactide-co-trimethylene carbonate),collagen, heparinized collagen, poly(caprolactone), poly(glycolic acid),and a copolymer.

[0095] In some embodiments, the outlet end further comprises a pluralityof pillars at the outlet end. In some embodiments, the bioactive agentis in or on at least one of the pillars.

[0096] In some embodiments, the implant is at least partially coatedwith at least one polymer film that contains the bioactive agent, thepolymer film permitting a delivery of a quantity of the bioactive agentto ocular tissues over time.

[0097] Some embodiments include an ocular implant comprising a bodyhaving a bioactive agent in or on the body, the body further comprisingan inlet section configured to be positioned in the anterior chamber ofan eye; an outlet section configured to be positioned at least partiallyin Schlemm's canal of the eye, the outlet section being in fluidcommunication with the inlet section; a lumen extending between theinlet section and the outlet section; and a flow-restricting memberwithin the lumen, the flow-restricting member being configured toprevent at least one component of blood from passing through theflow-restricting member.

[0098] In some embodiments, the bioactive agent comprises an Imidazoleantiproliferative agent, a quinoxaline, a phsophonylmethoxyalkylnucleotide analog, a potassium channel blocker, and/or a syntheticoligonucleotide. In some embodiments, the bioactive agent comprises5-[1-hydroxy-2-[2-(2-methoxyphenoxyl) ethylamino]ethyl]-2-methylbenzenesulfonamide.

[0099] In some embodiments, the bioactive agent comprises a guanylatecyclase inhibitor, such as methylene blue, butylated hydroxyanisole,and/or N-methylhydroxylamine. In some embodiments, the bioactive agentcomprises 2-(4-methylaminobutoxy) diphenylmethane. In some embodiments,the bioactive agent comprises a combination of apraclonidine andtimolol.

[0100] In some embodiments, the bioactive agent comprises a cloprostenolanalog or a fluprostenol analog. In some embodiments, the bioactiveagent comprises a crosslinked carboxy-containing polymer, a sugar, andwater. In some embodiments, the bioactive agent comprises anon-corneotoxic serine-threonine kinase inhibitor. In some embodiments,the bioactive agent comprises a nonsteroidal glucocorticoid antagonist.In some embodiments, the bioactive agent comprises a prostaglandinanalog or a derivative thereof.

[0101] These and other embodiments of the inventions will becomeapparent to those skilled in the art from the following detaileddescription of exemplary embodiments having reference to the attachedfigures, the inventions not being limited to any particular preferredembodiment(s) disclosed.

BRIEF DESCRIPTION OF THE DRAWINGS

[0102] Certain preferred embodiments and modifications thereof willbecome apparent to those skilled in the art from the detaileddescription herein having reference to the figures that follow, ofwhich:

[0103]FIG. 1 is a coronal cross-sectional view of an eye.

[0104]FIG. 2 is an enlarged cross-sectional view of an anterior chamberangle of the eye of FIG. 1 with a trabecular stent.

[0105]FIG. 3 is a schematic and partial sectional view of an eyeillustrating an implanted glaucoma stent in accordance with oneembodiment of at least one of the inventions disclosed herein.

[0106]FIG. 4 is a side elevational view of the stent of FIG. 3.

[0107]FIG. 5 is a top plan view of the stent of FIG. 3.

[0108]FIG. 6 is a bottom plan view of the stent of FIG. 3.

[0109]FIG. 7 is a front elevational view of the stent of FIG. 3 (alongline 7-7 of FIG. 4).

[0110]FIG. 8 is a rear elevational view of the stent of FIG. 3 (alongline 8-8 of FIG. 4).

[0111]FIG. 9 is an enlarged top plan view of a forward end of the stentof FIG. 3.

[0112]FIG. 10 is a top plan view of a modification of an inlet end ofthe stent of FIG. 3.

[0113]FIG. 11 is a top plan view of another modification of the inletend of the stent of FIG. 3.

[0114]FIG. 12 is a top plan view of yet another modification of theinlet end of the stent of FIG. 3.

[0115]FIG. 13 is a top plan view of still another modification of theinlet end of the stent of FIG. 3.

[0116]FIG. 14 is schematic and partial sectional view of an eyeillustrating a modification of the implanted glaucoma stent of FIG. 3.

[0117]FIG. 15 is a schematic and partial sectional view of an eyeillustrating a further modification of the implanted glaucoma stent ofFIG. 3.

[0118]FIG. 16 is a side elevational view of yet another modification ofthe glaucoma stent of FIG. 3.

[0119]FIG. 17 is a top plan view of the stent of FIG. 16.

[0120]FIG. 18 is a bottom plan view of the stent of FIG. 16.

[0121]FIG. 19 is a front elevational view along line 19-19 of FIG. 16.

[0122]FIG. 20 is a rear elevational view along line 20-20 of FIG. 16.

[0123]FIG. 21 is a side elevation view of still another modification ofthe glaucoma stent of FIG. 3.

[0124]FIG. 22 is a top plan view of the stent of FIG. 21.

[0125]FIG. 23 is a bottom plan view of the stent of FIG. 21.

[0126]FIG. 24 is a front elevational view along line 24-24 of FIG. 21.

[0127]FIG. 25 is a rear elevational view along line 25-25 of FIG. 21.

[0128]FIG. 26 is a front elevational view of a modification of theglaucoma stent illustrated in FIG. 3.

[0129]FIG. 27 is a right side elevational view of the stents illustratedin FIG. 26 as viewed along the line 27-27.

[0130]FIG. 28 is a right side elevational view of the glaucoma stentillustrated in FIG. 26, as viewed along the line 28-28.

[0131]FIG. 29 is a schematic and partial sectional view of an eyeillustrating a temporal implantation of a glaucoma stent using adelivery apparatus having features and advantages in accordance with atleast one of the inventions disclosed herein.

[0132]FIG. 30 is an oblique elevational view of an articulating armstent delivery/retrieval apparatus having features and advantages inaccordance with an embodiment of at least one of the inventionsdisclosed herein.

[0133]FIG. 31 is a schematic and partial sectional view of a portion ofan eye and illustrating an implantation of a glaucoma stent using adelivery apparatus extending through the anterior chamber of the eye.

[0134]FIG. 32 is a schematic and partial sectional view of a Schlemm'scanal and trabecular meshwork of an eye with another glaucoma stentextending from the anterior chamber of the eye, through the trabecularmeshwork, and into a rear wall of the Schlemm's canal.

[0135]FIG. 33 is an enlarged cross-sectional view of a distal portion ofthe stent illustrated in FIG. 32.

[0136]FIG. 34 is a schematic and partial sectional view of the eye ofFIG. 32 and a side elevational view of a modification of the stentillustrated in FIG. 32.

[0137]FIG. 35 is a schematic and partial sectional view of the eyeillustrated in FIG. 32, and a side elevational view of aphotomodification of the stent illustrated in FIG. 32.

[0138]FIG. 36 is a schematic and partial sectional view of the eyeillustrated in FIG. 32, and a side elevational view of anothermodification of the stent of FIG. 32.

[0139]FIG. 37 is a schematic and partial sectional view of the eyeillustrated in FIG. 32, and a side elevational view of a furthermodification of the implant illustrated in FIG. 32.

[0140]FIG. 38 is a schematic and partial sectional view of the eyeillustrated in FIG. 32 and a side elevational view of anothermodification of the stent illustrated in FIG. 32.

[0141]FIG. 39 is a schematic and partial sectional view of the eyeillustrated in FIG. 32, and a side elevational view of the furthermodification of the implant illustrated in FIG. 32.

[0142]FIG. 40 is a schematic and partial sectional view of the eyeillustrated in FIG. 32, and a side elevational view of yet anothermodification of the stent illustrated in FIG. 32.

[0143]FIG. 41 is a schematic and partial sectional view of an eye andthe side elevational view of yet another modification of the stentillustrated in FIG. 32.

[0144]FIG. 42 is a schematic and partial sectional view of the eyeillustrated in FIG. 32, and a side elevational view of yet anothermodification of the implant illustrated in FIG. 32.

[0145]FIG. 43 is an enlarged schematic and partial cross-sectional viewof an anterior chamber angle of an eye having a valve stent implantedtherein.

[0146]FIG. 44 is an enlarged cross-sectional view of an anterior chamberangle of an eye including an osmotic membrane device implanted therein.

[0147]FIG. 45 is an enlarged cross-sectional view of an anterior chamberangle of an eye illustrating an implantation of a glaucoma stent usingan ab externo procedure.

[0148]FIG. 46 is a schematic and partial sectional view of the eyeillustrated in FIG. 32 and a side elevational view of anothermodification of the implant illustrated in FIG. 32.

[0149]FIG. 47 is an enlarged schematic and partial sectional view of theeye illustrated in FIG. 32 and including a drug release device implantedtherein.

[0150]FIG. 48 is a flow diagram illustrating a method for treatingglaucoma.

[0151]FIG. 49A is an enlarged schematic illustration showing an anteriorchamber, trabecular meshwork and a Schlemm's canal of an eye and anoblique elevational view of yet another modification of the stentillustrated in FIG. 32.

[0152]FIG. 49B is an oblique elevational view of a modification of thestent illustrated in FIG. 49A.

[0153]FIG. 49C is a side elevational view of another modification of thestent illustrated in FIG. 49A.

[0154]FIG. 50A is a cross-sectional view of the eye portion showinganatomically the trabecular meshwork, Schlemm's canal and one collectorduct.

[0155]FIG. 50B is a cross-sectional view of FIG. 50A with a portion of astent mechanically inserted into one of the collector ducts.

[0156]FIG. 51A is a side elevational view of a stent delivery applicatorwith a steerable distal section for multiple stent deployment.

[0157]FIG. 51B is a schematic and partial sectional view of the distalsection of the stent delivery applicator of FIG. 51A.

[0158]FIG. 51C is a cross-sectional view, section 1-1 of FIG. 51B.

[0159]FIG. 51D is an oblique side elevational view of the steerablesection of the delivery applicator illustrated in FIG. 51A and includingan optional ultrasonically enabled distal end.

[0160]FIG. 52A is a partial sectional and side elevational view of adistal section of a modification of the stent delivery applicatorillustrated in FIG. 51A.

[0161]FIG. 52B is a partial sectional and side elevational view of adistal section of the stent delivery applicator illustrated in FIG. 51Ahaving been inserted through a trabecular meshwork with the stentdisposed within the distal section.

[0162]FIG. 52C is a partial sectional and side elevational view of adistal section of the stent delivery applicator illustrated in FIG. 51Ahaving been inserted through a trabecular meshwork and after the sheathof the distal portion has been withdrawn.

[0163]FIG. 52D is a partial sectional and side elevational view of adistal section of the stent delivery applicator illustrated in FIG. 51Ahaving been inserted through a trabecular meshwork, and after the sheathand a cutting member have been withdrawn.

[0164]FIG. 53 is an oblique side elevational and partial sectional viewof a further modification of the stent illustrated in FIG. 32.

[0165]FIG. 54A is a sectional view of yet another modification of thestent delivery applicator illustrated in FIG. 51A.

[0166]FIG. 54B is an enlarged sectional view of a distal end of theapplicator illustrated in FIG. 54A and including two implants disposedover a trocar of the device, this portion being identified by the circle2-2 in FIG. 54A.

[0167]FIG. 54C is a sectional view of the applicator device taken alongsection line 3-3 of FIG. 54A.

[0168]FIG. 55 shows an embodiment of a seton implant constructedaccording to the principles of the invention.

[0169]FIG. 56 is a top cross-sectional view of section 1-1 of FIG. 55.

[0170]FIG. 57 is another embodiment of a seton implant constructed inaccordance with the principles of the invention.

[0171]FIG. 58 is an oblique elevation view of one embodiment of atrabecular stenting device.

[0172]FIG. 59 is an oblique elevation view of another embodiment of atrabecular stenting device.

[0173]FIG. 60 is an oblique elevation view of placement of one end of atrabecular stenting device through a trabecular meshwork.

[0174]FIG. 61 is an oblique elevation view of placement of one end of atrabecular stenting device through a trabecular meshwork, wherein thetrabecular stenting device is passed over a guidewire.

[0175]FIG. 62 is an oblique elevation view of a preferred implantationof a trabecular stenting device through a trabecular meshwork.

[0176]FIG. 63 is a close-up, cut-away view of an inlet section of thetrabecular stenting device of FIGS. 58 and 59, illustrating aflow-restricting member retained within a lumen of the trabecularstenting device.

[0177]FIG. 64 is one embodiment of an axisymmetric trabecular stentingdevice for incorporating bioactive agents.

[0178]FIG. 65 is one embodiment of a fistula without a lumen fortransporting aqueous and carrying bioactive agents of the presentinvention.

DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS

[0179] The preferred embodiments described herein relate particularly tosurgical and therapeutic treatment of glaucoma through reduction ofintraocular pressure and/or stimulation of the trabecular meshworktissue. While the description sets forth various embodiment-specificdetails, it will be appreciated that the description is illustrativeonly and should not be construed in any way as limiting the invention.Furthermore, various applications of the inventions disclosed herein,and modifications thereto, which may occur to those who are skilled inthe art, are also encompassed by the general concepts described herein.

[0180]FIG. 1 is a cross-sectional view of an eye 10. FIG. 2 is anenlarged sectional view of the eye showing the relative anatomicallocations of a trabecular meshwork 21, an anterior chamber 20, and aSchlemm's canal 22. A sclera 11 is a thick collagenous tissue thatcovers the entire eye 10 except a portion that is covered by a cornea12.

[0181] With reference to FIGS. 1 and 2, the cornea 12 is a thintransparent tissue that focuses and transmits light into the eye andthrough a pupil 14, which is a circular hole in the center of an iris 13(colored portion of the eye). The cornea 12 merges into the sclera 11 ata juncture referred to as a limbus 15. A ciliary body 16 extends alongthe interior of the sclera 11 and is coextensive with a choroid 17. Thechoroid 17 is a vascular layer of the eye 10, located between the sclera11 and a retina 18. An optic nerve 19 transmits visual information tothe brain and is the anatomic structure that is progressively destroyedby glaucoma.

[0182] With continued reference to FIGS. 1 and 2, the anterior chamber20 of the eye 10, which is bound anteriorly by the cornea 12 andposteriorly by the iris 13 and a lens 26, is filled with aqueous humor(hereinafter referred to as “aqueous”). Aqueous is produced primarily bythe ciliary body 16, then moves anteriorly through the pupil 14 andreaches an anterior chamber angle 25, formed between the iris 13 and thecornea 12.

[0183] As best illustrated by the drawing of FIG. 2, in a normal eye,aqueous is removed from the anterior chamber 20 through the trabecularmeshwork 21. Aqueous passes through the trabecular meshwork 21 intoSchlemm's canal 22 and thereafter through a plurality of collector ductsand aqueous veins 23, which merge with blood-carrying veins, and intosystemic venous circulation. Intraocular pressure is maintained by anintricate balance between secretion and outflow of aqueous in the mannerdescribed above. Glaucoma is, in most cases, characterized by anexcessive buildup of aqueous in the anterior chamber 20, which leads toan increase in intraocular pressure. Fluids are relativelyincompressible, and thus intraocular pressure is distributed relativelyuniformly throughout the eye 10.

[0184] As shown in FIG. 2, the trabecular meshwork 21 is adjacent asmall portion of the sclera 11. Exterior to the sclera 11 is aconjunctiva 24. Traditional procedures that create a hole or opening forimplanting a device through the tissues of the conjunctiva 24 and sclera11 involve extensive surgery, as compared to surgery for implanting adevice, as described herein, which ultimately resides entirely withinthe confines of the sclera 11 and cornea 12. A trabecular stent 229 canbe placed bypassing the trabecular meshwork 21 with a proximal terminal227 exposed to anterior chamber 20 and a distal terminal 228 exposed toSchlemm's canal 22.

[0185]FIG. 3 schematically illustrates the use of one embodiment of atrabecular stenting device 30 for establishing an outflow pathway,passing through the trabecular meshwork 21, described in greater detailbelow. FIGS. 4-9 are different views of the stent 30. Advantageously,and as discussed in further detail later herein, theself-trephining-stent allows a one-step procedure to make an incision inthe trabecular mesh 21 and place the stent or implant 30 at the desiredor predetermined position within the eye 10. Desirably, this facilitatesand simplifies the overall surgical procedure.

[0186] In the illustrated embodiment of FIGS. 3-9, the shunt or stent 30generally comprises an inlet portion or “snorkel” 32 and a main bodyportion or blade 34. The snorkel 32 and blade 34 are mechanicallyconnected to or in mechanical communication with one another. Agenerally longitudinal axis 36 extends along the stent 30 and/or thebody portion 34.

[0187] In the illustrated embodiment of FIGS. 3-9, the stent 30comprises an integral unit. In modified embodiments, the stent 30 maycomprise an assembly of individual pieces or components. For example,the stent 30 may comprise an assembly of the snorkel 32 and blade 34.

[0188] In the illustrated embodiment of FIGS. 3-9, the snorkel 32 is inthe form of a generally elongate tubular member and generally comprisesan upper seat, head or cap portion 38, a shank portion 40 and a lumen orpassage 42 extending therethrough. The seat 38 is mechanically connectedto or in mechanical communication with the shank 40, which is alsomechanically connected to, or in mechanical communication with the blade34. The longitudinal axis 43 extends along the snorkel 32 and/or thelumen 42.

[0189] In the illustrated embodiment of FIGS. 3-9, the seat 38 isgenerally circular in shape and has an upper surface 44 and a lowersurface 46, which, as shown in FIG. 3, abuts or rests against thetrabecular meshwork 21 to stabilize the glaucoma stent 30 within the eye10. In modified embodiments, the seat 38 may efficaciously be shaped inother suitable manners, as required or desired, giving due considerationto the goals of stabilizing the glaucoma stent 30 within the eye 10and/or of achieving one or more of the benefits and advantages as taughtor suggested herein. For example, the seat 38 may be shaped in otherpolygonal or non-polygonal shapes and/or comprise one or more ridgeswhich extend radially outwards, among other suitable retention devices.

[0190] In the illustrated embodiment of FIGS. 3-9, and as best seen inthe top view of FIG. 5, the seat top surface 44 comprises fiducial marksor indicia 48. These marks or indicia 48 facilitate and ensure properorientation and alignment of the stent 30 when implanted in the eye 10.The marks or indicia 48 may comprise visual differentiation means suchas color contrast or be in the form of ribs, grooves, or the like.Alternatively, or in addition, the marks 48 may provide tactile sensoryfeedback to the surgeon by incorporating a radiopaque detectable orultrasound imaginable substrate at about the mark 48. Also, the seat 38and/or the seat top surface 44 may be configured in predetermined shapesaligned with the blade 34 and/or longitudinal axis 36 to provide forproper orientation of the stent device 30 within the eye 10. Forexample, the seat top surface 44 may be oval or ellipsoidal (FIG. 10),rectangular (FIG. 11), hexagonal (FIG. 12), among other suitable shapes(e.g. FIG. 13).

[0191] In the illustrated embodiment of FIGS. 3-9, and as indicatedabove, the seat bottom surface 46 abuts or rests against the trabecularmeshwork 21 to stabilize and retain the glaucoma stent 30 within the eye10. For stabilization purposes, the seat bottom surface 46 may comprisea studded surface, a ribbed surface, a surface with pillars, a texturedsurface, or the like.

[0192] In the illustrated embodiment of FIGS. 3-9, the snorkel shank 40is generally cylindrical in shape. With the stent 30 implanted, as shownin FIG. 3, the shank 40 is generally positioned in an incision or cavity50 formed in the trabecular meshwork 21 by the self-trephining stent 30.Advantageously, and as discussed further below, this single step offorming the cavity 50 by the stent 30 itself and placing the stent 30 inthe desired position facilitates and expedites the overall surgicalprocedure. In modified embodiments, the snorkel shank 40 mayefficaciously be shaped in other suitable manners, as required ordesired. For example, the shank 40 may be in the shape of otherpolygonal or non-polygonal shapes, such as, oval, ellipsoidal, and thelike.

[0193] In the illustrated embodiment of FIGS. 3-9, and as best seen inFIG. 3, the shank 40 has an outer surface 52 in contact with thetrabecular meshwork 21 surrounding the cavity 50. For stabilizationpurposes, the shank outer surface 52 may comprise a studded surface, aribbed surface, a surface with pillars, a textured surface, or the like.

[0194] In the illustrated embodiment of FIGS. 3-9, the snorkel lumen 42has an inlet port, opening or orifice 54 at the seat top surface 44 andan outlet port, opening or orifice 56 at the junction of the shank 40and blade 34. The lumen 42 is generally cylindrical in shape, that is,it has a generally circular cross-section, and its ports 54, 56 aregenerally circular in shape. In modified embodiments, the lumen 42 andports 54, 56 may be efficaciously shaped in other manners, as requiredor desired, giving due consideration to the goals of providingsufficient aqueous outflow and/or of achieving one or more of thebenefits and advantages as taught or suggested herein. For example, thelumen 42 and/or one or both ports 54, 56 may be shaped in the form ofovals, ellipsoids, and the like, or the lumen 42 may have a tapered orstepped configuration.

[0195] Referring in particular to FIG. 3, aqueous from the anteriorchamber 20 flows into the lumen 42 through the inlet port 54 (asgenerally indicated by arrow 58) and out of the outlet port 56 and intoSchlemm's canal 22 (as generally indicated by arrows 60) to lower and/orbalance the intraocular pressure (IOP). In another embodiment, asdiscussed in further detail below, one or more of the outlet ports maybe configured to face in the general direction of the stent longitudinalaxis 36. In modified embodiments, the snorkel 32 may comprise more thanone lumen, as needed or desired, to facilitate multiple aqueous outflowtransportation into Schlemm's canal 22.

[0196] In the illustrated embodiment of FIGS. 3-9, the bladelongitudinal axis 36 and the snorkel longitudinal axis 43 are generallyperpendicular to one another. Stated differently, the projections of theaxes 36, 43 on a common plane which is not perpendicular to either ofthe axes 36, 43 intersect at 90°. The blade longitudinal axis 36 and thesnorkel longitudinal axis 43 may intersect one another or may be offsetfrom one another.

[0197] In the illustrated embodiment of FIGS. 3-9, the main body portionor blade 34 is a generally curved elongated sheet- or plate-likestructure with an upper curved surface 62 and a lower curved surface 64,which defines a trough or open face channel 66. The perimeter of theblade 34 is generally defined by a curved proximal edge 68 proximate tothe snorkel 32, a curved distal edge 70 spaced from the proximal edge 68by a pair of generally straight lateral edges 72, 74. The first lateraledge 72 extends beyond the second lateral edge 74 and intersects withthe distal edge 70 at a distal-most point 76 of the blade 34.Preferably, the blade 34 defines a blade cutting tip 78.

[0198] In the illustrated embodiment of FIGS. 3-9, and as shown in theenlarged view of FIG. 9, the cutting tip 78 comprises a first cuttingedge 80 on the distal edge 70 and a second cutting edge 82 on thelateral edge 72. The cutting edges 80, 82 preferably extend from thedistal-most point 76 of the blade 34 and comprise at least a respectiveportion of the distal edge 70 and lateral edge 72. The respectivecutting edges 80, 82 are formed at the sharp edges of respective beveledor tapered surfaces 84, 86. In one embodiment, the remainder of thedistal edge 70 and lateral edge 72 are dull or rounded. In oneembodiment, the tip 78 proximate to the distal-most end 76 is curvedslightly inwards, as indicated generally by the arrow 88 in FIG. 5 andarrow 88 (pointed perpendicular and into the plane of the paper) in FIG.9, relative to the adjacent curvature of the blade 34.

[0199] In modified embodiments, suitable cutting edges may be providedon selected portions of one or more selected blade edges 68, 70, 72, 74with efficacy, as needed or desired, giving due consideration to thegoals of providing suitable cutting means on the stent 30 foreffectively cutting through the trabecular meshwork 21 (FIG. 3) and/orof achieving one or more of the benefits and advantages as taught orsuggested herein.

[0200] Referring in particular to FIG. 9, in one embodiment, the ratiobetween the lengths of the cutting edges 80, 82 is about 2:1. In anotherembodiment, the ratio between the lengths of the cutting edges 80, 82 isabout 1:1. In yet another embodiment, the ratio between the lengths ofthe cutting edges 80, 82 is about 1:2. In modified embodiments, thelengths of the cutting edges 80, 82 may be efficaciously selected inother manners, as required or desired, giving due consideration to thegoals of providing suitable cutting means on the stent 30 foreffectively cutting through the trabecular meshwork 21 (FIG. 3) and/orof achieving one or more of the benefits and advantages as taught orsuggested herein.

[0201] Still referring in particular to FIG. 9, in one embodiment, theratio between the lengths of the cutting edges 80, 82 is in the rangefrom about 2:1 to about 1:2. In another embodiment, the ratio betweenthe lengths of the cutting edges 80, 82 is in the range from about 5:1to about 1:5. In yet another embodiment, the ratio between the lengthsof the cutting edges 80, 82 is in the range from about 10:1 to about1:10. In modified embodiments, the lengths of the cutting edges 80, 82may be efficaciously selected in other manners, as required or desired,giving due consideration to the goals of providing suitable cuttingmeans on the stent 30 for effectively cutting through the trabecularmeshwork 21 (FIG. 3) and/or of achieving one or more of the benefits andadvantages as taught or suggested herein.

[0202] As shown in the top view of FIG. 9, the cutting edge 80 (and/orthe distal end 70) and the cutting edge 82 (and/or the lateral edge 72)intersect at an angle θ. Stated differently, θ is the angle between theprojections of the cutting edge 80 (and/or the distal end 70) and thecutting edge 82 (and/or the lateral edge 72) on a common plane that isnot perpendicular to either of these edges.

[0203] Referring to in particular to FIG. 9, in one embodiment, theangle θis about 50°. In another embodiment, the angle θis in the rangefrom about 40° to about 60°. In yet another embodiment, the angle θis inthe range from about 30° to about 70°. In modified embodiments, theangle θ may be efficaciously selected in other manners, as required ordesired, giving due consideration to the goals of providing suitablecutting means on the stent 30 for effectively cutting through thetrabecular meshwork 21 (FIG. 3) and/or of achieving one or more of thebenefits and advantages as taught or suggested herein.

[0204] The stent 30 of the embodiments disclosed herein can bedimensioned in a wide variety of manners. Referring in particular toFIG. 3, the depth of Schlemm's canal 22 is typically about less than 400microns (μm). Accordingly, the stunt blade 34 is dimensioned so that theheight of the blade 34 (referred to as H₄₁ in FIG. 4) is typically lessthan about 400 μm. The snorkel shank 40 is dimensioned so that it has alength (referred to as L₄₁ in FIG. 4) typically in the range from about150 μm to about 400 μm, which is roughly the typical range of thethickness of the trabecular meshwork 21.

[0205] Of course, as the skilled artisan will appreciate, that with thestent 30 implanted, the blade 34 may rest at any suitable positionwithin Schlemm's canal 22. For example, the blade 34 may be adjacent toa front wall 90 of Schlemm's canal 22 (as shown in FIG. 3), or adjacentto a back wall 92 of Schlemm's canal 22, or at some intermediatelocation therebetween, as needed or desired. Also, the snorkel shank 40may extend into Schlemm's canal 22. The length of the snorkel shank 40and/or the dimensions of the blade 34 may be efficaciously adjusted toachieve the desired implant positioning.

[0206] The trabecular stenting device 30 (FIGS. 3-9) of the exemplaryembodiment may be manufactured or fabricated by a wide variety oftechniques. These include, without limitation, molding, thermo-forming,or other micro-machining techniques, among other suitable techniques.

[0207] The trabecular stenting device 30 preferably comprises abiocompatible material such that inflammation arising due to irritationbetween the outer surface of the device 30 and the surrounding tissue isminimized. Biocompatible materials which may be used for the device 30preferably include, but are not limited to, titanium, titanium alloys,medical grade silicone, e.g., Silastic™, available from Dow CorningCorporation of Midland, Mich.; and polyurethane, e.g., Pellethane™, alsoavailable from Dow Corning Corporation.

[0208] In other embodiments, the stent device 30 may comprise othertypes of biocompatible material, such as, by way of example, polyvinylalcohol, polyvinyl pyrolidone, collagen, heparinized collagen,polytetrafluoroethylene, expanded polytetrafluoroethylene, fluorinatedpolymer, fluorinated elastomer, flexible fused silica, polyolefin,polyester, polysilicon, and/or a mixture of the aforementionedbiocompatible materials, and the like. In still other embodiments,composite biocompatible material may be used, wherein a surface materialmay be used in addition to one or more of the aforementioned materials.For example, such a surface material may include polytetrafluoroethylene(PTFE) (such as Teflon™), polyimide, hydrogel, heparin, therapeuticdrugs (such as beta-adrenergic antagonists and other anti-glaucomadrugs, or antibiotics), and the like.

[0209] In an exemplary embodiment of the trabecular meshwork surgery,the patient is placed in the supine position, prepped, draped andanesthetized as necessary. A small (less than about 1 mm) incision,which may be self sealing, can then be made through the cornea 12. Thecorneal incision can be made in a number of ways, for example, by usinga micro-knife, among other tools.

[0210] An applicator or delivery apparatus is used to advance theglaucoma stent 30 through the corneal incision and to the trabecularmeshwork 21. Some embodiments of such a delivery apparatus are disclosedin copending U.S. application Ser. No. 10/101,548, filed Mar. 18, 2002,entitled APPLICATOR AND METHODS FOR PLACING A TRABECULAR SHUNT FORGLAUCOMA TREATMENT, and U.S. Provisional Application No. 60/276,609,filed Mar. 16, 2001, entitled APPLICATOR AND METHODS FOR PLACING ATRABECULAR SHUNT FOR GLAUCOMA TREATMENT, the entire contents of each oneof which are hereby incorporated by reference herein. Some embodimentsof a delivery apparatus are also described in further detail below.Gonioscopic, microscopic, or endoscopic guidance can be used during thetrabecular meshwork surgery.

[0211] With the device 30 held by the delivery apparatus, the blade 34of the device 30 is used to cut and/or displace the material of thetrabecular meshwork 21. The snorkel shank 40 can also facilitate inremoval of this material during implantation. The delivery apparatus iswithdrawn once the device 30 has been implanted in the eye 10. As shownin FIG. 3, the snorkel seat 38 can rest on a top surface 94 of thetrabecular meshwork 21 with the snorkel shank 40 extending through thecavity 50 (created by the device 30) in the trabecular meshwork 21, andwith the blade 34 extending inside Schlemm's canal 22.

[0212] Advantageously, the embodiments of the self-trephining stentdevice 30 allow for a “one-step” procedure to make an incision in thetrabecular meshwork and to implant the stent in the proper orientationand alignment within the eye to allow outflow of aqueous from theanterior chamber through the stent and into Schlemm's canal to lowerand/or balance the intraocular pressure (IOP). Desirably, this providesfor a faster, safer, and less expensive surgical procedure.

[0213] Many complications can arise in trabecular meshwork surgeries,wherein a knife is first used to create an incision in the trabecularmeshwork, followed by removal of the knife and subsequent installationof the stent. For instance, the knife may cause some bleeding whichclouds up the surgical site. This may require more effort and time toclean the surgical site prior to placement of the stent. Moreover, thismay cause the intraocular pressure (IOP) to rise or to fall undesirably.Thus, undesirably, such a multiple step procedure may demand crisismanagement that slows down the surgery, makes it less safe, and moreexpensive.

[0214]FIG. 14 is a simplified partial view of an eye 10 illustrating theimplantation of a self-trephining glaucoma stent device 30 a havingfeatures and advantages in accordance with one embodiment. The stent 30a is generally similar to the stent 30 of FIGS. 3-9 except that itssnorkel 32 a comprises a longer shank 40 a, which extends into Schlemm'scanal 22 and a lumen 42 a, which bifurcates into two output channels 45a.

[0215] In the illustrated embodiment of FIG. 14, the shank 40 aterminates at the blade 34. Aqueous flows from the anterior chamber 20into the lumen 42 a through an inlet port 54 a (as generally indicatedby arrow 58 a). Aqueous then flows through the output channels 45 a andout of respective outlet ports 56 a and into Schlemm's canal 22 (asgenerally indicated by arrows 60 a). The outlet channels 45 a extendradially outwards in generally opposed directions and the outlet ports56 a are configured to face in the general direction of the stentlongitudinal axis 36 so that they open into Schlemm's canal 22 and arein proper orientation to allow aqueous outflow into Schlemm's canal 22for lowering and/or balancing the intraocular pressure (IOP). Asindicated above, fiducial marks or indicia and/or predetermined shapesof the snorkel seat 38 allow for proper orientation of the blade 34 andalso the output channels 45 a and respective ports 56 a within Schlemm'scanal.

[0216] In the illustrated embodiment of FIG. 14, two outflow channels 45a are provided. In another embodiment, only one outflow channel 45 a isprovided. In yet another embodiment, more than two outflow channels 45 aare provided. In modified embodiments, the lumen 42 a may extend all theway through to the blade 34 and provide an outlet port as discussedabove with reference to the embodiment of FIGS. 3-9.

[0217]FIG. 15 is a simplified partial view of an eye 10 illustrating theimplantation of a self-trephining glaucoma stent device 30 b havingfeatures and advantages in accordance with one embodiment. The stent 30b is generally similar to the stent 30 of FIGS. 3-9 except that itssnorkel 32 b comprises a longer shank 40 b, which extends into Schlemm'scanal 22 and a lumen 42 b, which bifurcates into two output channels 45b.

[0218] In the illustrated embodiment of FIG. 15, the shank 40 b extendsthrough the blade 34. Aqueous flows from the anterior chamber 20 intothe lumen 42 b through an inlet port 54 b (as generally indicated byarrow 58 b). Aqueous then flows through the output channels 45 b and outof respective outlet ports 56 b and into Schlemm's canal 22 (asgenerally indicated by arrows 60 b). The outlet channels 45 b extendradially outwards in generally opposed directions and the outlet ports56 b are configured to face in the general direction of the stentlongitudinal axis 36 so that they open into Schlemm's canal 22 and arein proper orientation to allow aqueous outflow into Schlemm's canal 22for lowering and/or balancing the intraocular pressure (IOP). Asindicated above, fiducial marks or indicia and/or predetermined shapesof the snorkel seat 38 allow for proper orientation of the blade 34 andalso the output channels 45 b and respective ports 56 b within Schlemm'scanal.

[0219] In the illustrated embodiment of FIG. 15, two outflow channels 45b are provided. In another embodiment, only one outflow channel 45 b isprovided. In yet another embodiment, more than two outflow channels 45 bare provided. In modified embodiments, the lumen 42 b may extend all theway through to the blade 34 and provide an outlet port as discussedabove with reference to the embodiment of FIGS. 3-9.

[0220] FIGS. 16-20 show different views of a self-trephining glaucomastent device 30 c having features and advantages in accordance with oneembodiment. The stent 30 c is generally similar to the stent 30 of FIGS.3-9 except that it has a modified blade configuration. The stent 30 ccomprises a blade 34 c which is a generally curved elongated sheet- orplate-like structure with an upper curved surface 62 c and a lowercurved surface 64 c which defines a trough or open face channel 66 c.The perimeter of the blade 34 c is generally defined by a curvedproximal edge 68 c proximate to the snorkel 32, a curved distal edge 70c spaced from the proximal edge 68 c by a pair of generally straightlateral edges 72 c, 74 c which are generally parallel to one another andhave about the same length.

[0221] In the illustrated embodiment of FIGS. 16-20, the blade 34 ccomprises a cutting tip 78 c. The cutting tip 78 c preferably includescutting edges formed on selected portions of the distal edge 70 c andadjacent portions of the lateral edges 72 c, 74 c for cutting throughthe trabecular meshwork for placement of the snorkel 32. The cuttingedges are sharp edges of beveled or tapered surfaces as discussed abovein reference to FIG. 9. The embodiment of FIGS. 16-20 may beefficaciously modified to incorporate the snorkel configuration of theembodiments of FIGS. 14 and 15.

[0222] FIGS. 21-25 show different views of a self-trephining glaucomastent device 30 d having features and advantages in accordance with oneembodiment. The stent 30 d is generally similar to the stent 30 of FIGS.3-9 except that it has a modified blade configuration. The stent 30 dcomprises a blade 34 d which is a generally curved elongated sheet- orplate-like structure with an upper curved surface 62 d and a lowercurved surface 64 d which defines a trough or open face channel 66 d.The perimeter of the blade 34 d is generally defined by a curvedproximal edge 68 d proximate to the snorkel 32, a pair of inwardlyconverging curved distal edges 70 d′, 70 d″ spaced from the proximaledge 68 d by a pair of generally straight respective lateral edges 72 d,74 d which are generally parallel to one another and have about the samelength. The distal edges 70 d′, 70 d″ intersect at a distal-most point76 d of the blade 34 d proximate a blade cutting tip 78 d.

[0223] In the illustrated embodiment of FIGS. 21-25, the cutting tip 78d preferably includes cutting edges formed on the distal edges 70 d′, 70d″ and extending from the distal-most point 76 d of the blade 34 d. Inone embodiment, the cutting edges extend along only a portion ofrespective distal edges 70 d′, 70 d.″ In another embodiment, the cuttingedges extend along substantially the entire length of respective distaledges 70 d′, 70 d.″ In yet another embodiment, at least portions of thelateral edges 72 d, 74 d proximate to respective distal edges 70 d′, 70d″ have cutting edges. In a further embodiment, the tip 78 d proximateto the distal-most end 76 d is curved slightly inwards, as indicatedgenerally by the arrow 88 d in FIG. 21 and arrow 88 d (pointedperpendicular and into the plane of the paper) in FIG. 22, relative tothe adjacent curvature of the blade 34 d.

[0224] In the embodiment of FIGS. 21-25, the cutting edges are sharpedges of beveled or tapered surfaces as discussed above in reference toFIG. 9. The embodiment of FIGS. 21-25 may be efficaciously modified toincorporate the snorkel configuration of the embodiments of FIGS. 14 and15.

[0225] FIGS. 26-28 show different views of a self-trephining glaucomastent device 30 e having features and advantages in accordance with oneembodiment. The stent device 30 e generally comprises a snorkel 32 emechanically connected to or in mechanical communication with a blade orcutting tip 34 e. The snorkel 32 e has a seat, head or cap portion 38 emechanically connected to or in mechanical communication with a shank 40e, as discussed above. The shank 40 e has a distal end or base 47 e. Thesnorkel 32 e further has a lumen 42 e, which bifurcates into a pair ofoutlet channels 45 e, as discussed above in connection with FIGS. 14 and15. Other lumen and inlet and outlet port configurations as taught orsuggested herein may also be efficaciously used, as needed or desired.

[0226] In the illustrated embodiment of FIGS. 26-28, the blade 34 eextends downwardly and outwardly from the shank distal end 47 e. Theblade 34 e is angled relative to a generally longitudinal axis 43 e ofthe snorkel 32 e, as best seen in FIGS. 27 and 28. The blade 34 e has adistal-most point 76 e. The blade or cutting tip 34 e has a pair of sideedges 70 e′, 70 e,″ including cutting edges, terminating at thedistal-most point 76 e, as best seen in FIG. 26. In one embodiment, thecutting edges are sharp edges of beveled or tapered surfaces asdiscussed above in reference to FIG. 9.

[0227] Referring to FIGS. 26-28, in one embodiment, the blade 34 eincludes cutting edges formed on the edges 70 e′, 70 e″ and extendingfrom the distal-most point 76 e of the blade 34 d. In one embodiment,the cutting edges extend along only a portion of respective distal edges70 e′, 70 e.″ In another embodiment, the cutting edges extend alongsubstantially the entire length of respective distal edges 70 e′, 70 e.″In yet another embodiment, the blade or cutting tip 34 e comprises abent tip of needle, for example, a 30 gauge needle.

[0228] In general, any of the blade configurations disclosed herein maybe used in conjunction with any of the snorkel configurations disclosedherein or incorporated by reference herein to provide a self-trephiningglaucoma stent device for making an incision in the trabecular meshworkfor receiving the corresponding snorkel to provide a pathway for aqueousoutflow from the eye anterior chamber to Schlemm's canal, therebyeffectively lowering and/or balancing the intraocular pressure (IOP).The self-trephining ability of the device, advantageously, allows for a“one-step” procedure in which the incision and placement of the snorkelare accomplished by a single device and operation. In any of theembodiments, fiducial markings or indicia, and/or preselectedconfiguration of the snorkel seat, and/or positioning of the stentdevice in a preloaded applicator may be used for proper orientation andalignment of the device during implantation.

[0229] In many cases, a surgeon works from a temporal incision whenperforming cataract or goniometry surgery. FIG. 29 illustrates atemporal implant procedure, wherein a delivery apparatus or “applicator”100 having a curved tip 102 is used to deliver a stent 30 to a temporalside 27 of the eye 10. An incision 28 is made in the cornea 10, asdiscussed above. The apparatus 100 is then used to introduce the stent30 through the incision 28 and implant it within the eye 10.

[0230] Still referring in particular to FIG. 29, in one embodiment, asimilarly curved instrument would be used to make the incision throughthe trabecular meshwork 21. In other embodiments, a self-trephiningstent device 30 may be used to make this incision through the trabecularmeshwork 21, as discussed above. The temporal implantation procedureillustrated in FIG. 29 may be employed with the any of the various stentembodiments taught or suggested herein.

[0231]FIG. 30 illustrates one embodiment of an apparatus comprising anarticulating stent applicator or retrieval device 100 a. In thisembodiment, a proximal arm 106 is attached to a distal arm 108 at ajoint 112. This joint 112 is movable such that an angle formed betweenthe proximal arm 106 and the distal arm 108 can change. One or moreclaws 114 can extend from the distal arm 108, in the case of a stentretrieval device. Similarly, this articulation mechanism may be used forthe trabecular stent applicator, and thus the articulating applicator orretrieval device 100 a may be either an applicator for the trabecularstent, a retrieval device, or both, in various embodiments. Theembodiment of FIG. 30 may be employed with the any of the various stentembodiments taught or suggested herein.

[0232]FIG. 31 shows another illustrative method for placing any of thevarious stent embodiments taught or suggested herein at the implant sitewithin the eye 10. A delivery apparatus 100 b generally comprises asyringe portion 116 and a cannula portion 118. The distal section of thecannula 118 has at least one irrigating hole 120 and a distal space 122for holding the stent device 30. The proximal end 124 of the lumen ofthe distal space 122 is sealed from the remaining lumen of the cannulaportion 118. The delivery apparatus of FIG. 30 may be employed with theany of the various stent embodiments taught or suggested herein.

[0233] In one aspect of the invention, a delivery apparatus (or“applicator”) is used for placing a trabecular stent through atrabecular meshwork of an eye. Certain embodiments of such a deliveryapparatus are disclosed in copending U.S. application Ser. No.10/101,548, filed Mar. 18, 2002, entitled APPLICATOR AND METHODS FORPLACING A TRABECULAR SHUNT FOR GLAUCOMA TREATMENT, and U.S. ProvisionalApplication No. 60/276,609, filed Mar. 16, 2001, entitled APPLICATOR ANDMETHODS FOR PLACING A TRABECULAR SHUNT FOR GLAUCOMA TREATMENT, theentire contents of each one of which are hereby incorporated byreference herein.

[0234] The stent has an inlet section and an outlet section. Thedelivery apparatus includes a handpiece, an elongate tip, a holder andan actuator. The handpiece has a distal end and a proximal end. Theelongate tip is connected to the distal end of the handpiece. Theelongate tip has a distal portion and is configured to be placed througha corneal incision and into an anterior chamber of the eye. The holderis attached to the distal portion of the elongate tip. The holder isconfigured to hold and release the inlet section of the trabecularstent. The actuator is on the handpiece and actuates the holder torelease the inlet section of the trabecular stent from the holder. Whenthe trabecular stent is deployed from the delivery apparatus into theeye, the outlet section is positioned in substantially oppositedirections inside Schlemm's canal. In one embodiment, a deploymentmechanism within the delivery apparatus includes a push-pull typeplunger.

[0235] In some embodiments, the holder comprises a clamp. In someembodiments, the apparatus further comprises a spring within thehandpiece that is configured to be loaded when the stent is being heldby the holder, the spring being at least partially unloaded uponactuating the actuator, allowing for release of the stent from theholder.

[0236] In various embodiments, the clamp comprises a plurality of clawsconfigured to exert a clamping force onto the inlet section of thestent. The holder may also comprise a plurality of flanges.

[0237] In some embodiments, the distal portion of the elongate tip ismade of a flexible material. This can be a flexible wire. The distalportion can have a deflection range, preferably of about 45 degrees fromthe long axis of the handpiece.

[0238] The delivery apparatus can further comprise an irrigation port inthe elongate tip.

[0239] Some aspects include a method of placing a trabecular stentthrough a trabecular meshwork of an eye, the stent having an inletsection and an outlet section, including advancing a delivery apparatusholding the trabecular stent through an anterior chamber of the eye andinto the trabecular meshwork, placing part of the stent through thetrabecular meshwork and into a Schlemm's canal of the eye; and releasingthe stent from the delivery apparatus.

[0240] In various embodiments, the method includes using a deliveryapparatus that comprises a handpiece having a distal end and a proximalend; an elongate tip connected to the distal end of the handpiece, theelongate tip having a distal portion and being configured to be placedthrough a corneal incision and into an anterior chamber of the eye; aholder attached to the distal portion of the elongate tip, the holderconfigured to hold and release the inlet section of the trabecularstent; and an actuator on the handpiece that actuates the holder torelease the inlet section of the trabecular stent from the holder.

[0241] In one aspect, the trabecular stent is removably attached to adelivery apparatus (also known as “applicator”). When the trabecularstent is deployed from the delivery apparatus into the eye, the outletsection is positioned in substantially opposite directions insideSchlemm's canal. In one embodiment, a deployment mechanism within thedelivery apparatus includes a push-pull type plunger. In someembodiments, the delivery applicator may be a guidewire, an expandablebasket, an inflatable balloon, or the like.

[0242] Screw/Barb Anchored Stent

[0243]FIGS. 32 and 33 illustrate a glaucoma stent device 30 f havingfeatures and advantages in accordance with one embodiment. Thisembodiment of the trabecular stent 30 f includes a barbed or threadedscrew-like extension or pin 126 with barbs 128 for anchoring. The barbedpin 126 extends from a distal or base portion 130 of the stent 30 f.

[0244] In use, the stent 30 f (FIG. 32) is advanced through thetrabecular meshwork 21 and across Schlemm's canal 22. The barbed (orthreaded) extension 126 penetrates into the back wall 92 of Schlemm'scanal 22 up to the shoulder or base 130 that then rests on the back wall92 of the canal 22. The combination of a shoulder 130 and a barbed pin126 of a particular length limits the penetration depth of the barbedpin 126 to a predetermined or preselected distance. In one embodiment,the length of the pin 126 is about 0.5 mm or less. Advantageously, thisbarbed configuration provides a secure anchoring of the stent 30 f. Asdiscussed above, correct orientation of the stent 30 f is ensured byappropriate fiducial marks, indicia or the like and by positioning ofthe stent in a preloaded applicator.

[0245] Referring to FIG. 32, the aqueous flows from the anterior chamber20, through the lumen 42 f, then out through two side-ports 56 f to bedirected in both directions along Schlemm's canal 22. Alternatively,flow could be directed in only one direction through a single side-port56 f. In other embodiments, more then two outlet ports 56 f, forexample, six to eight ports (like a pin wheel configuration), may beefficaciously used, as needed or desired.

[0246] Still referring to FIG. 32, in one embodiment, the stent 30 f isinserted through a previously made incision in the trabecular meshwork21. In other embodiments, the stent 30 f may be combined with any of theblade configurations taught or suggested herein to provideself-trephining capability. In these cases, the incision through thetrabecular meshwork 21 is made by the self-trephining stent device thathas a blade at its base or proximate to the base.

[0247] Deeply Threaded Stent

[0248]FIG. 34 illustrates a glaucoma stent device 30 g having featuresand advantages in accordance with one embodiment. The stent 30 g has ahead or seat 38 g and a shank or main body portion 40 g with a base ordistal end 132. This embodiment of the trabecular stent 30 g includes adeep thread 134 (with threads 136) on the main body 40 g of the stent 30g below the head 38 g. The threads may or may not extend all the way tothe base 132.

[0249] In use, the stent 30 g (FIG. 34) is advanced through the meshwork21 through a rotating motion, as with a conventional screw.Advantageously, the deep threads 136 provide retention and stabilizationof the stent 30 g in the trabecular meshwork 21.

[0250] Referring to FIG. 34, the aqueous flows from the anterior chamber20, through the lumen 42 g, then out through two side-ports 56 g to bedirected in both directions along Schlemm's canal 22. Alternatively,flow could be directed in only one direction through a single side-port56 g. In other embodiments, more then two outlet ports 56 g may beefficaciously used, as needed or desired.

[0251] One suitable applicator or delivery apparatus for this stent 30 g(FIG. 34) includes a preset rotation, for example, via a wound torsionspring or the like. The rotation is initiated by a release trigger onthe applicator. A final twist of the applicator by the surgeon andobservation of suitable fiducial marks, indicia or the like ensureproper alignment of the side ports 56 g with Schlemm's canal 22.

[0252] Referring to FIG. 34, in one embodiment, the stent 30 g isinserted through a previously made incision in the trabecular meshwork21. In other embodiments, the stent 30 g may be combined with any of theblade configurations taught or suggested herein to provideself-trephining capability. In these cases, the incision through thetrabecular meshwork 21 is made by the self-trephining stent device thathas a blade at its base or proximate to the base.

[0253] Rivet Style Stent

[0254]FIG. 35 illustrates a glaucoma stent device 30 h having featuresand advantages in accordance with one embodiment. The stent has a baseor distal end 138. This embodiment of the trabecular stent 30 h has apair of flexible ribs 140. In the unused state, the ribs are initiallygenerally straight (that is, extend in the general direction of arrow142).

[0255] Referring to FIG. 35, upon insertion of the stent 30 h throughthe trabecular meshwork 21, the ends 144 of respective ribs 140 of thestent 30 h come to rest on the back wall 92 of Schlemm's canal 22.Further advancement of the stent 30 h causes the ribs 140 to deform tothe bent shape as shown in the drawing of FIG. 35. The ribs 140 aredesigned to first buckle near the base 138 of the stent 30 h. Then thebuckling point moves up the ribs 140 as the shank part 40 h of the stent30 h is further advanced through the trabecular meshwork 21.

[0256] The lumen 42 h (FIG. 35) in the stent 30 h is a simple straighthole. The aqueous flows from the anterior chamber 20, through the lumen42 h, then out around the ribs 140 to the collector channels furtheralong Schlemm's canal 22 in either direction.

[0257] Referring to FIG. 35, in one embodiment, the stent 30 h isinserted through a previously made incision in the trabecular meshwork21. In other embodiments, the stent 30 h may be combined with any of theblade configurations taught or suggested herein to provideself-trephining capability. In these cases, the incision through thetrabecular meshwork 2.1 is made by the self-trephining stent device thathas a blade at its base or proximate to the base.

[0258] Grommet Style Stent

[0259]FIG. 36 illustrates a glaucoma stent device 30 i having featuresand advantages in accordance with one embodiment. This embodiment of thetrabecular stent 30 i includes a head or seat 38 i, a tapered baseportion 146 and an intermediate narrower waist portion or shank 40 i.

[0260] In use, the stent 30 i (FIG. 36) is advanced through thetrabecular meshwork 21 and the base 146 is pushed into Schlemm's canal22. The stent 30 i is pushed slightly further, if necessary, until themeshwork 21 stretched by the tapered base 146 relaxes back and thencontracts to engage the smaller diameter portion waist 40 i of the stent30 i. Advantageously, the combination of the larger diameter head orseat 38 i and base 146 of the stent 30 i constrains undesirable stentmovement. As discussed above, correct orientation of the stent 30 i isensured by appropriate fiducial marks, indicia or the like and bypositioning of the stent in a preloaded applicator.

[0261] Referring to FIG. 36, the aqueous flows from the anterior chamber20, through the lumen 42 i, then out through two side-ports 56 i to bedirected in both directions along Schlemm's canal 22. Alternatively,flow could be directed in only one direction through a single side-port56 i. In other embodiments, more then two outlet ports 56 i may beefficaciously used, as needed or desired.

[0262] Still referring to FIG. 36, in one embodiment, the stent 30 i isinserted through a previously made incision in the trabecular meshwork21. In other embodiments, the stent 30 i may be combined with any of theblade configurations taught or suggested herein to provideself-trephining capability. In these cases, the incision through thetrabecular meshwork 21 is made by the self-trephining stent device,which has a blade at its base or proximate to the base.

[0263] Biointeractive Stent

[0264]FIG. 37 illustrates a glaucoma stent device 30 j having featuresand advantages in accordance with one embodiment. This embodiment of thetrabecular stent 30 j utilizes a region of biointeractive material 148that provides a site for the trabecular meshwork 21 to firmly grip thestent 30 j by ingrowth of the tissue into the biointeractive material148. As shown in FIG. 37, preferably the biointeractive layer 148 isapplied to those surfaces of the stent 30 j, which would abut against orcome in contact with the trabecular meshwork 21.

[0265] In one embodiment, the biointeractive layer 148 (FIG. 37) may bea region of enhanced porosity with a growth promoting chemical. In oneembodiment, a type of bio-glue 150 that dissolves over time is used tohold the stent secure during the time between insertion and sufficientingrowth for stabilization. As discussed above, correct orientation ofthe stent 30 j is ensured by appropriate fiducial marks, indicia or thelike and by positioning of the stent in a preloaded applicator.

[0266] Referring to FIG. 37, the aqueous flows from the anterior chamber20, through the lumen 42 j, then out through two side-ports 56 j to bedirected in both directions along Schlemm's canal 22. Alternatively,flow could be directed in only one direction through a single side-port56 j. In other embodiments, more then two outlet ports 56 j may beefficaciously used, as needed or desired.

[0267] Still referring to FIG. 37, in one embodiment, the stent 30 j isinserted through a previously made incision in the trabecular meshwork21. In other embodiments, the stent 30 j may be combined with any of theblade configurations taught or suggested herein to provideself-trephining capability. In these cases, the incision through thetrabecular meshwork 21 is made by the self-trephining stent device,which has a blade at its base or proximate to the base.

[0268] Glued or Welded Stent

[0269]FIG. 38 illustrates a glaucoma stent device 30 k having featuresand advantages in accordance with one embodiment. This embodiment of thetrabecular stent 30 k is secured in place by using a permanent(non-dissolving) bio-glue 152 or a “welding” process (e.g., heat) toform a weld 152. The stent 30 k has a head or seat 38 k and a lowersurface 46 k.

[0270] The stent 30 k is advanced through the trabecular meshwork 21until the head or seat 38 k comes to rest on the trabecular meshwork 21,that is, the head lower surface 46 k abuts against the trabecularmeshwork 21, and the glue or weld 152 is applied or formed therebetween,as shown in FIG. 38. As discussed above, correct orientation of thestent 30 k is ensured by appropriate fiducial marks, indicia or the likeand by positioning of the stent in a preloaded applicator.

[0271] Referring to FIG. 38, the aqueous flows from the anterior chamber20, through the lumen 42 k, then out through two side-ports 56 k to bedirected in both directions along Schlemm's canal 22. Alternatively,flow could be directed in only one direction through a single side-port56 k. In other embodiments, more then two outlet ports 56 k may beefficaciously used, as needed or desired.

[0272] Still referring to FIG. 38, in one embodiment, the stent 30 k isinserted through a previously made incision in the trabecular meshwork21. In other embodiments, the stent 30 k may be combined with any of theblade configurations taught or suggested herein to provideself-trephining capability. In these cases, the incision through thetrabecular meshwork 21 is made by the self-trephining stent device,which has a blade at its base or proximate to the base.

[0273] Hydrophilic Latching Stent

[0274]FIG. 39 illustrates a glaucoma stent device 30 m having featuresand advantages in accordance with one embodiment. This embodiment of thetrabecular stent 30 m is fabricated from a hydrophilic material thatexpands with absorption of water. Desirably, this would enable thedevice 30 m to be inserted through a smaller incision in the trabecularmeshwork 21. The subsequent expansion (illustrated by the smaller arrows154) of the stent 30 m would advantageously enable it to latch in placein the trabecular meshwork 21. As discussed above, correct orientationof the stent 30 m is ensured by appropriate fiducial marks, indicia orthe like and by positioning of the stent in a preloaded applicator.

[0275] Referring to FIG. 39, the aqueous flows from the anterior chamber20, through the lumen 42 m, then out through two side-ports 56 m to bedirected in both directions along Schlemm's canal 22. Alternatively,flow could be directed in only one direction through a single side-port56 m. In other embodiments, more then two outlet ports 56 m may beefficaciously used, as needed or desired.

[0276] Still referring to FIG. 39, in one embodiment, the stent 30 m isinserted through a previously made incision in the trabecular meshwork21. In other embodiments, the stent 30 m may be combined with any of theblade configurations taught or suggested herein to provideself-trephining capability. In these cases, the incision through thetrabecular meshwork 21 is made by the self-trephining stent device,which has a blade at its base or proximate to the base.

[0277] Photodynamic Stent

[0278]FIG. 40 illustrates a glaucoma stent device 30 n having featuresand advantages in accordance with one embodiment. This embodiment of thetrabecular stent 30 n is fabricated from a photodynamic material thatexpands on exposure to light.

[0279] It is commonly known that there is a diurnal variation in theaqueous humor production by the eye—it is higher during the day than itis at night. The lumen 42 n of the stent 30 n responds to light enteringthe cornea during the day by expanding and allowing higher flow ofaqueous through the lumen 42 n and into Schlemm's canal 22. Thisexpansion is generally indicated by the smaller arrows 156 (FIG. 40)which show the lumen 42 n (and ports) expanding or opening in responseto light stimulus. (The light or radiation energy E is generally givenby E=hv, where h is Planck's constant and v is the frequency of thelight provided.) At night, in darkness, the lumen diameter decreases andreduces the flow allowed through the lumen 42 n. In one embodiment, anexcitation wavelength that is different from that commonly encounteredis provided on an as-needed basis to provide higher flow of aqueous toSchlemm's canal 22.

[0280] This photodynamic implementation is shown in FIG. 40 for theself-latching style of stent 30 n, but can be efficaciously used withany of the other stent embodiments, as needed or desired. As discussedabove, correct orientation of the stent 30 n is ensured by appropriatefiducial marks, indicia or the like and by positioning of the stent in apreloaded applicator.

[0281] Referring to FIG. 40, the aqueous flows from the anterior chamber20, through the lumen 42 n, then out through two side-ports 56 n to bedirected in both directions along Schlemm's canal 22. Alternatively,flow could be directed in only one direction through a single side-port56 n. In other embodiments, more then two outlet ports 56 n may beefficaciously used, as needed or desired.

[0282] Still referring to FIG. 40, in one embodiment, the stent 30 n isinserted through a previously made incision in the trabecular meshwork21. In other embodiments, the stent 30 n may be combined with any of theblade configurations taught or suggested herein to provideself-trephining capability. In these cases, the incision through thetrabecular meshwork 21 is made by the self-trephining stent device,which has a blade at its base or proximate to the base.

[0283] Collector Channel Alignment Stent

[0284]FIG. 41 illustrates a glaucoma stent device 30 p having featuresand advantages in accordance with one embodiment. This figure depicts anembodiment of a stent 30 p that directs aqueous from the anteriorchamber 20 directly into a collector channel 29, which empties intoaqueous veins. The stent 30 p has a base or distal end 160.

[0285] In the illustrated embodiment of FIG. 41, a removable alignmentpin 158 is utilized to align the stent lumen 42 p with the collectorchannel 29. In use, the pin 158 extends through the stent lumen 42 p andprotrudes through the base 160 and extends into the collector channel 29to center and/or align the stent 30 p over the collector channel 29. Thestent 30 p is then pressed firmly against the back wall 92 of Schlemm'scanal 22. A permanent bio-glue 162 is used between the stent base andthe back wall 92 of Schlemm's canal 22 to seat and securely hold thestent 30 p in place. Once positioned, the pin 158 is withdrawn from thelumen 42 p to allow the aqueous to flow directly from the anteriorchamber 20 into the collector duct 29. The collector ducts are nominally20 to 100 micrometers (μm) in diameter and are visualized with asuitable microscopy method (such as ultrasound biomicroscopy (UBM)) orlaser imaging to provide guidance for placement of the stent 30 p.

[0286] Referring to FIG. 41, in one embodiment, the stent 30 p isinserted through a previously made incision in the trabecular meshwork21. In other embodiments, the stent 30 p may be combined with any of theblade configurations taught or suggested herein to provideself-trephining capability. In these cases, the incision through thetrabecular meshwork 21 is made by the self-trephining stent device,which has a blade at its base or proximate to the base.

[0287] Barbed Stent (Anterior Chamber to Collector Channel)

[0288]FIG. 42 illustrates a glaucoma stent device 30 q having featuresand advantages in accordance with one embodiment. This figure depicts anembodiment of a stent 30 q that directs aqueous from the anteriorchamber 20 directly into a collector channel 29, which empties intoaqueous veins. The stent 30 q has a base or distal end 166 and thechannel 29 has wall(s) 164.

[0289] In the illustrated embodiment of FIG. 42, a barbed,small-diameter extension or pin 168 on the stent base 166 is guided intothe collector channel 29 and anchors on the wall(s) 164 of the channel29. The pin 168 has barbs 170 which advantageously provide anchoring ofthe stent 30 q. The collector ducts 29 are nominally 20 to 100micrometers (μm) in diameter and are visualized with a suitablemicroscopy method (such as ultrasound biomicroscopy (UBM)) or laserimaging to provide guidance for placement of the stent.

[0290] Referring to FIG. 42, in one embodiment, the stent 30 q isinserted through a previously made incision in the trabecular meshwork21. In other embodiments, the stent 30 q may be combined with any of theblade configurations taught or suggested herein to provideself-trephining capability. In these cases, the incision through thetrabecular meshwork 21 is made by the self-trephining stent device,which has a blade at its base or proximate to the base.

[0291] Valved Tube Stent (Anterior Chamber to Choroid)

[0292]FIG. 43 illustrates a valved tube stent device 30 r havingfeatures and advantages in accordance with one embodiment. This is anembodiment of a stent 30 r that provides a channel for flow between theanterior chamber 20 and the highly vascular choroid 17. Clinically, thechoroid 17 can be at pressures lower than those desired for the eye 10.Therefore, this stent 30 r includes a valve with an opening pressureequal to the desired pressure difference between the choroid 17 and theanterior chamber 10 or a constriction that provide the desired pressuredrop.

[0293] Osmotic Membrane (Anterior Chamber to Choroid)

[0294]FIG. 44 illustrates a osmotic membrane device 30 s having featuresand advantages in accordance with one embodiment. This embodimentprovides a channel for flow between the anterior chamber 20 and thehighly vascular choroid 17. The osmotic membrane 30 s is used to replacea portion of the endothelial layer of the choroid 17. Since the choroid17 is highly vascular with blood vessels, the concentration of water onthe choroid side is lower than in the anterior chamber 20 of the eye 10.Therefore, the osmotic gradient drives water from the anterior chamber20 into the choroid 17.

[0295] Clinically, the choroid 17 (FIG. 44) can be at pressures lowerthan those desired for the eye 10. Therefore, desirably, both osmoticpressure and the physical pressure gradient are in favor of flow intothe choroid 17. Flow control is provided by proper sizing of the area ofthe membrane; the larger the membrane area is the larger the flow ratewill be. This advantageously enables tailoring to tune the flow to thedesired physiological rates.

[0296] Ab Externo Insertion of Stent via Small Puncture

[0297]FIG. 45 illustrates the implantation of a stent 30 t using an abexterno procedure having features and advantages in accordance with oneembodiment. In the ab externo procedure of FIG. 45, the stent 30 t isinserted into Schlemm's canal 21 with the aid of an applicator ordelivery apparatus 100 c that creates a small puncture into the eye 10from outside.

[0298] Referring to FIG. 45, the stent 30 t is housed in the applicator100 c, and pushed out of the applicator 100 c once the applicator tip isin position within the trabecular meshwork 21. Since the tissuesurrounding the trabecular meshwork 21 is optically opaque, an imagingtechnique, such as ultrasound biomicroscopy (UBM) or a laser imagingtechnique, is utilized. The imaging provides guidance for the insertionof the applicator tip and the deployment of the stent 30 t. Thistechnique can be used with a large variety of stent embodiments withslight modifications since the trabecular meshwork 21 is punctured fromthe scleral side rather than the anterior chamber side in the ab externoinsertion.

[0299]FIG. 46 a glaucoma stent device 30 u having features andadvantages in accordance with a modified embodiment. This grommet-stylestent 30 u for ab externo insertion is a modification of the embodimentof FIG. 36. In the embodiment of FIG. 46, the upper part or head 38 u istapered while the lower part or base 172 is flat, as opposed to theembodiment of FIG. 36. The stent 30 u is inserted from the outside ofthe eye 10 through a puncture in the sclera. Many of the otherembodiments of stents taught or suggested herein can be modified forsimilar implantation.

[0300] This ultra microscopic device 30 u (FIG. 46) can be used with (1)a targeting Lasik-type laser, or with (2) contact on eyes or with (3)combined ultrasound microscope or (4) other device inserter handpiece.

[0301] Targeted Drug Delivery to the Trabecular Meshwork

[0302]FIG. 47 illustrates a targeted drug delivery implant 30 v havingfeatures and advantages in accordance with one embodiment. This drawingis a depiction of a targeted drug delivery concept. The slow releaseimplant 30 v is implanted within the trabecular meshwork 21.

[0303] A drug that is designed to target the trabecular meshwork 21 toincrease its porosity, or improve the active transport across theendothelial layer of Schlemm's canal 22 can be stored in this smallimplant 30 v (FIG. 47). Advantageously, slow release of the drugpromotes the desired physiology at minimal dosage levels since the drugis released into the very structure that it is designed to modify.

[0304] Dose Response

[0305] The programmed (also know as “Targeted”) stent placement refersto the intentional placement of a stent or stents at a particularlocation or locations in Schlemm's canal for the purpose of providing abenefit in the form of more optimal outflow. For example, a method canbe provided which includes assessing the aqueous flow characteristics ofan eye. Such characteristics can include, for example, but withoutlimitation, collector channel distribution, collector channel flowcharacteristics, outflow resistance, outflow capacity,shape/size/tortuosity of Schlemm's canal, and other factors). The methodcan also include determining an optimal stent placement and implantingstents in one or plurality of positions and procedures. For example, thedetermination of the desired stent placement can include considerationof a database of cadaver anatomy regarding the number and location ofcollector channels, the patient's micro-anatomy data, the number ofstents to be used, the type of stents to be used, the location of anypreviously implanted stents whether the desired stent is drug-loaded,gene-loaded or surface treated, and/or any associated drug therapy.

[0306]FIG. 48 includes a flow diagram illustrating a decision tree fordetermining desired stent placement. In the illustrated embodiment,after it is determined that a patient is suffering from excess ofintraocular pressure (IOP), a bypass flow model is determined to aid inthe decision of whether or not to use single or multiple stents.Optionally, the configuration of collector channels in the patient's eyecan be met to aid in the creation of a bypass flow model. Further, otherinformation can be used, such as, for example, but without limitation,outflow resistance, aqueous production, and venous pressure.

[0307] The bypass flow model, which can be based on the above-notedinformation, is determined so as to provide a desired strategy forlowering the excessive intraocular pressure. If it is decided that asingle stent should be used, an optimized stent location is firstdetermined based on the bypass flow model. The implantation of thesingle stent results in reduced IOP. After this implantation, it isagain determined if there is a need for further reduction in IOP. Ifadditional IOP reduction is desired, then a further bypass flow model iscreated. For example, the second bypass flow model can be determined inthe same or similar manner as the first bypass flow model describedabove. In light of the second bypass flow model, an additional stent canbe implanted at an optimized location to further reduce IOP.

[0308] If it is determined, in light of the first bypass flow model,that multiple stents should be used, the location of the multiple stentsis first optimized. Then, the multiple stents are implanted. Afterwards,it is again determined if additional intraocular pressure reduction isneeded, and the trimming can continue as noted above.

[0309] Where additional stents are implanted in light of the secondbypass flow model, the additional stents can be different from the firststents implanted. For example, where single or multiple stents areimplanted in accordance with the first bypass flow model, the additionalstents can be of a different type. For example, in one embodiment, thefirst stent is a G1 (First generation) trabecular stent that has beendisclosed in copending applications and the second stent(s) is the sameG1 trabecular stent. In another embodiment, the second stent(s) isdifferent from the first stent; for example, the second stent is a G2stent (that is, “injectable axisymmetric stent”; a second generationstent). In still another embodiment, the second stent(s) is smaller than(in some case, larger than) the first stent. The dose response may alsorelate to the stent configuration or characteristics such asdrug-loading or surface treatment enabling enhancing aqueous transportor therapeutic effects on the tissue as needed. Drug-loaded ordrug-eluting stent may comprise different types of drugs including, butnot limited to, those cited in copending patent application Ser. No.10/046,137 filed Nov. 8, 2001, entitled DRUG RELEASING TRABECULARIMPLANT FOR GLAUCOMA TREATMENT, the entire contents of which is herebyincorporated by reference.

[0310] With reference to FIG. 49A, a stent extending between an anteriorchamber 20 of an eye, through the trabecular meshwork 21, and intoSchlemm's canal 22 of an eye can be configured to be axisymmetric withrespect to the flow of aqueous therethrough. For example, as shown inFIG. 49A, the stent 229A comprises an inlet end 230 configured to bedisposed in the anterior chamber 20. The second end 231 of the stent229A is configured to be disposed in Schlemm's canal 22.

[0311] At least one lumen 239 extends through the stent 229A between theinlet and outlet ends 230, 232. The lumen 239 defines an opening 232 atthe inlet end 230 as well as an outlet 233 at the outlet end 231.

[0312] In the illustrated embodiment, an exterior surface 238 of thestent 229A is cone-shaped. Thus, a circumference of the exterior surface238 adjacent to the inlet end 230 is smaller than the circumference ofthe outer surface 238 at the outlet end 231.

[0313] With the stent 229A extending through the trabecular meshwork 21,the tissue of the trabecular meshwork 221 provides additional anchoringforce for retaining the stent 229A with its inlet end 230 in theanterior chamber and its outlet end 231 in Schlemm's canal. For example,the trabecular meshwork 21 would naturally tend to close an apertureoccupied by the stent 229A. As such, the trabecular meshwork 221 wouldtend to squeeze the stent 229A. Because the exterior surface 238 isconical, the squeezing force applied by the trabecular meshwork 221would tend to draw the stent 229A towards Schlemm's canal 22. In theillustrated embodiment, the stent 229A is sized such that a portion 234of the stent 229 adjacent to the inlet end 230 remains in the anteriorchamber 20 while a portion 235 of the stent 229 adjacent to the outletend 231 remains in Schlemm's canal 22.

[0314] In the illustrated embodiment, the outer surface 238 of the stent229A is straight. Alternatively, the outer surface 238 can have othercontours such as, for example, but without limitation curved or stepped.In one embodiment, the outer surface 238 can be curved in a concavemanner so as to produce a trumpet-like shape. Alternatively, the outersurface 238 can be convex.

[0315] The stent 229A preferably includes one or plurality of posts orlegs 236 configured to maintain a space between the outlet opening 233and a wall of Schlemm's canal 22. As such, the legs 236 prevent a wallof Schlemm's canal from completely closing off the outlet opening 233 ofthe stent 229A. In the illustrated embodiment, the legs 236 are coupledto the distal-most surface of the stent 229A and are substantiallyparallel to an implant axis extending through the stent 229A and betweenthe anterior chamber 20 and Schlemm's canal 22.

[0316] This arrangement of the legs 236 and the outlet 233 imparts anaxisymmetric flow characteristic to the stent 229A. For example, aqueouscan flow from the outlet 233 in any direction. Thus, the stent 229A canbe implanted into Schlemm's canal at any angular position relative toits implant axis. Thus, it is not necessary to determine the angularorientation of the stent 229A prior to implantation, nor is it necessaryto preserve a particular orientation during an implantation procedure.

[0317]FIG. 49B illustrates a modification of the stent 229A, identifiedgenerally by the reference numeral 229B. In this embodiment, the stent229B includes a flange 237 extending radially from the portion 234.Preferably, the flange 237 is configured to retain the first portion 234within the anterior chamber 20. It is to be recognized that althoughgenerally, aqueous will flow from the anterior chamber 20 towardsSchlemm's canal 22, the stent 229A, 229B or any of the above-describedstents as well as other stents described below, can provide foromni-directional flow of aqueous.

[0318]FIG. 49C illustrates another modification of the stent 229A,identified generally by the reference numeral 229C. In this embodiment,the outer surface 238C is not conical. Rather, the outer surface 238C iscylindrical. The stent 229C includes a flange 240 that can be the samesize and shape as the flange 237. The legs 236C extend from the flange240.

[0319] Constructed as such, the natural tendency of the tissue of thetrabecular meshwork 21 to close the hole in which the stent 229C isdisposed, aids in anchoring the stent 229C in place. Additionally, thelegs 236C aid in preventing the walls of Schlemm's canal from completelyclosing the outlet 233C of the lumen 239C.

[0320] Device for Mechanically Distending Collector Duct

[0321]FIG. 50A is an enlarged cross-sectional view of a portion of theeye 10 showing, anatomically, the trabecular meshwork 21, Schlemm'scanal 22, and a collector duct 23 in a natural state. FIG. 50B shows astent 229C extending into and thereby distending the collector duct 23.

[0322] The collector duct 23 has an inner diameter identified generallyby the reference numeral D₁, when in a relaxed or natural state. Becausethe collector duct 23 is not typically perfectly round, the diameter D1can correspond to an “equivalent” diameter. As used herein, theequivalent diameter can be determined by dividing the circumference ofthe inner surface of the collector duct 23 by π.

[0323] The stent 229D is sized to extend from the anterior chamber 20and into the collector duct 23. Thus, in the illustrated embodiment, thestent 229D includes an upstream end portion 230D and a downstream endportion 243.

[0324] The upstream portion 230D is configured to open into the anteriorchamber 20. The stent 229D is sized so as to extend from the anteriorchamber 20 and into the collector duct 23. In the illustratedembodiment, the stent 229D is sized so as to extend from the anteriorchamber 20, through the trabecular meshwork 21, through a portion ofSchlemm's canal 22, and into the collector duct 23. However, it isconceived that the stent 229D could bypass Schlemm's canal 22 and extenddirectly into a portion of the collector duct 23 downstream fromSchlemm's canal 22.

[0325] The downstream end portion 243 can have an outer diameter D₂ thatis larger that the diameter D₁. Preferably, the end potion 243 is sizedand configured for easy insertion into a collect duct 23 withoutinjuring the tissue or tissue surface of the collector duct 23. Thus,when the end portion 243 is disposed in the collector duct 23, thecollector duct 23 is distended, i.e., enlarged. As such, the resistanceagainst the outflow of aqueous provided by the collector duct 23 in itsnatural state can be reduced, thereby reducing IOP.

[0326] Preferably, the end portion 243 has a diameter D₂ substantiallylarger than the equivalent diameter D₁ of the duct 23 so as to deformthe collector duct beyond its elastic threshold into plastic deformationregion. As such, the collector duct 23 can aid in anchoring the stent229D in place.

[0327] Applicator for Multiple Stent Implantation

[0328]FIG. 51A is a perspective view of a stent delivery applicator 201configured for multiple stent deployment. The delivery applicator 201comprises an injection sheath 246 defining a stent lumen 249, a distalstent-holding section 259, and a handle 205.

[0329] The handle 205 includes an outer surface preferably configured tobe grasped by a human hand. Additionally, the handle can comprise astent delivery button 203. By way of example, the stent delivery button203 is configured to cause a stent discharge mechanism to discharge,from the applicator sheath 246, one stent at a time. The applicator 201can be configured to store and discharge a plurality of any combinationof the stents 229, 30, 30 a, 30 b, 30 c, 30 d, 30 e, 30 f, 30 g, 30 h,30 i, 30 j, 30 k, 30 m, 30 n, 30 p, 30 q, 30 r, 30 s, 30 t, 30 u, 30 v,229A, 229B, 229C, and 229D described above, the additional stentsdescribed below, or any other ocular stent or implant. In theillustrated embodiment, the applicator 201 is loaded with a plurality ofthe stents 229C

[0330] The applicator 201 can include other features as well, forexample, but without limitation, an optional connector 209 forconnecting to an external ultrasound power source, a fluid infusing port204 for fluid infusion or viscocanalostomy, and a steering mechanismcontrol device 202 configured to control the steering of a steerablesection 251 of the applicator 201.

[0331] The steerable section 251 can be configured to deflect the distalstent-holding section 259 about at least one axis. Optionally, thesteerable section 251 can configured to deflect the distal stent-holdingsection 259 about at least two axes, one axis being substantiallyperpendicular to the other. Thus, the portion of the sheath 246 thatdefines part of the steerable section 251 is flexible. Generally,similar steering mechanisms for deflecting a portion of an medicaldevice, such as endoscopes, are well-known in the art.

[0332] With reference to FIG. 51B, in the illustrated embodiment, thesteering actuator 202 is connected to a plurality of pulling wires 256A,256B. The wires 256A, 256B have distal portions 253A, 253B,respectively, disposed distally from the handle 205. The end 252A of thedistal wire portion 253A of the first pulling wire 256A is attached toone side of an inner surface of the sheath 246. The second pulling wire256B has its end 252B of the distal wire portion 253B attached to theopposite side of the inner surface of the sheath 246. The wire ends 252Aand 252B are disposed within the steerable distal section 251.

[0333] With reference to FIG. 51C, a relatively rigid guide 254 isdisposed in the lumen at an appropriate location proximal to the wireends 252A, 252B. The guide is configured to guide the pull wires 256A,256B such that the sheath 246 is deflected when the pull wires 256A,256B are pulled. In the illustrated embodiment, the guide 254 is in theform of a plate member.

[0334] The guide 254 can include holes 255A, 255B through which thepulling wires 253A, 253B extend. The guide 254 and the points at whichthe wire ends 252A, 25B are spaced. As such, when the pull wires 253A,253B are pulled by actuation of the steering actuator 202, the distalend of the sheath 246 is deflected. For example, as shown in FIG. 51D,when the wire 256A is pulled, the sheath deflects from Position I toPosition II.

[0335] As noted above, the delivery apparatus 201 can be configured todischarge a plurality of stents, one at a time, for implantation. In theillustrated embodiment, as shown in FIG. 51B, the delivery apparatus 201includes a plunger 244 connected with the stent delivery button 203. Theplunger 244 can comprise one or a plurality of plunger bodies that arejoined at the distal plunger end 244B. The distal plunger end 244B has agenerally round configuration and smooth surface adapted for evenlypushing a stent, such as the stent 229C, out of the sheath during adeployment phase of an implantation procedure.

[0336] As noted above, the sheath 246 defines a lumen 249 having aplunger 244. A space between the plunger 244 and the distal end 242 isreserved for storing a plurality of stents. The sheath 246 includes atleast one holding member 245 for each stent 229C stored therein. Theholding members 245 are configured to retain the stents 229C in placeduring storage and use, and to allow the stents 229C to pass when thestent 229C is pushed by the plunger 244.

[0337] In the illustrated embodiment, the sheath 146 includes a row of aplurality of holding members 245 upstream and downstream from each stent229C stored in the sheath 246. Thus, each stent 229C is prevented fromunintentionally moving in the upstream and downstream directions.

[0338]FIG. 51B illustrates two stents 229C being stored in the sheath246. However, it is conceived that the sheath 246 and holding members245 can be configured to hold one, three, or more stents 229C within thestent-holding distal end 259.

[0339] The holding member 245 can be a wire configured to exerted aforce to hold the stents 229C in place during storage and use, until theplunger 244 is moved to discharge a stent 229C from the end 242. Forexample, the wire can be made from a spring metal, an elasticallydeformable plastic, or other material, sized and shaped to retain thestents 229C during storage, and to allow the stents 229C to pass under aforce that can be generated by or applied to the plunger 244, toward theend 242. In the illustrated embodiment, the wires forming the holdingmembers 245 extend generally parallel to and convexly into the lumen249, and thus define stops for preventing unintentional movement of thestents 229C.

[0340] Alternatively, the holding members 245 can be in the form of amechanically or electronically actuatable gate. Such a gate can beconfigured to move from a closed position in which the stents 229C areretained in the storage positions, and an open position in which thestents 229C can be moved in the downstream direction. A mechanical gatecan be formed from members that can be moved or deflected radially fromthe inner surface of the lumen 249, under the control of a pull wire(not shown). An electronic gate can also include radially moveable ordeflectable members controlled by an electronic actuator, such as, forexample, but without limitation, solenoids, stepper motors, servomotors, and piezoelectric modules.

[0341] Alternatively, piezoelectric modules can be used to form theholding members. For example, small piezoelectric modules can be mountedon the inner surface of the sheath 246 to form stops when in a lockedposition. The piezoelectric modules can be connected to a power supplywith conduits. Thus, when actuated, the piezoelectric modules cancontract so as to move to an open position in which the stents 229C canpass.

[0342] As noted above, the applicator 201 preferably is configured toeject one stent at a time from the end 242. Thus, the applicator 201 canbe configured to move the plunger 244 a predetermined distance each timethe button 203 is depressed. For example, the button can be mechanicallyconnected to the plunger 244 so as to move the plunger 244 downstreamthrough the sheath 246 over the predetermined distance. Thepredetermined distance can be, for example, equal to about the length ofthe stent 229C.

[0343] Alternatively, the plunger can be driven by an electronicactuator (not shown) configured to eject one stent 229C at a time fromthe sheath 246. For example, the electronic actuator can be configuredto drive the plunger 244 over the predetermined distance each time thebutton 203 is depressed. The electronic actuator can be, for example butwithout limitation, solenoids, stepper motors, servo motors, andpiezoelectric modules. Driver electronics (not shown) can be configuredto drive the actuator so as to urge the plunger 244 over thepredetermined distance.

[0344] Preferably, the end 242 of the sheath 246 is sharpened to definea cutting (microtrephining) tip for creating a hole within thetrabecular meshwork 21 for stent placement. Thus, the applicator 201 canbe used for cutting the trabecular meshwork 21 and for implantingstents.

[0345] A further advantage is provided where the applicator includes anillumination feature for illuminating at least a portion of theimplantation site. For example, the illumination feature can beconfigured to generally illuminate the site at which a stent is to beimplanted. Optionally, the illumination feature can be configured togenerate a reticule for aligning the applicator with the desiredimplantation site. In one embodiment, a light source is provided to thetip section 242 of the stent applicator 201 wherein either laser lightis provided for cutting/spotting or fiber optic light is provided forillumination.

[0346] For example, but without limitation, the illumination feature cancomprise a small diameter light pipe or optic fiber element configuredto emit a fine point or beam of light and configured to be introducedab-internally. Additionally, the face or lens of the pipe or element canbe configured to be placed against the trabecular meshwork. In oneembodiment, the light pipe or optic fiber is the construct material ofthe sheath 246 of the stent delivery applicator 241A for multiple stentdeployment as shown in FIG. 51B. In another embodiment, the light pipeor optic fiber is snugly inserted within the lumen 249 of the applicatorsheath 246 or over the outer periphery of the applicator sheath 246.Optionally, the illumination device can be configured such that thepoint or beam emitting from the light tube would be highly visible fromthe outside of the eye and serve to guide the implantation of a stent.

[0347] As an alternative to including an illumination feature with theapplicator 201, simple non-invasive trans-scleral illumination, if ofthe proper intensity and wavelength, perhaps in a darkened environment,could silhouette the Schlemm's canal, trabecular meshwork, or moreprobably, the scleral spur with sufficient resolution to enableab-externo placement of a device into Schlemm's canal. In this case,blood could be backed up in a retrograde manner into Schlemm's canal bythe surgeon to provide additional optical density. Imaging means for abinternally imaging the anatomic structures for TBS stent implantationusing ultrasound imaging, laser imaging, OCT imaging or multi-wavelengthscanning can also be provided.

[0348] A further advantage is provided where the applicator 201 alsoincludes an imaging feature. For example, where the applicator 201includes an imaging feature for transmitting a video representation ofan implantation site of a stent to a user of the applicator, animplantation procedure can be further simplified. The imaging featurecan utilize any type of known imaging techniques, including, forexample, but without limitation, optical, and ultrasonic. In oneembodiment, an endoscope is mounted at the tip section 242 of the stentapplicator 201 for visualization during stent deployment and/orimplantation.

[0349]FIG. 51D shows one embodiment of the applicator 201 of FIG. 51Ahaving an ultrasonic imaging system. The illustrated embodiment of theimaging system is included on an applicator with a steerable section.However, it is to be noted that the imaging system can be used on anapplicator that does not have a steerable section.

[0350] In one embodiment, the ultrasonic imaging system comprises twoultrasonic probes or transducers 206, 207. The transducers 206, 207 canbe formed from an ultrasound ring or ultrasound tape. Preferably, thetransducers 206, 207 are located adjacent to the distal end 242 of thedelivery apparatus 201. As such, the transducers 206, 207 can move withthe distal end 242 during an implantation procedure.

[0351] The ultrasonic transducers 206, 207 are connected by flexiblewires (not shown) through the interior void 243 of the apparatus orthrough within the sheath 246 to the connector 209 located at the handle205 so that the ultrasonic signals are directed outwardly and receivedinwardly relative to the transducers 206, 207. For example, one of thetransducers 206, 207 can be configured to emit ultrasonic energy, andthe other can be configured to absorb the reflected portion of theemitted ultrasonic energy and to produce a signal indicative of theabsorbed energy.

[0352] In order to enhance the viewing and positioning of the distal end242 of the apparatus, an ultrasonic marker 208, which is visible toultrasonic energy, can be mounted at about the distal end 242 of theapplicator 201. For example, but without limitation, such a marker 208can be in the form of one or a plurality of encapsulated air bubbles. Inone illustrative example, the bubble in a marker 208 can be formed byintroducing air by a syringe (not shown) penetrating the wall of thesheath 246 and thereafter sealing the hole created by the syringe withepoxy.

[0353] Optionally, a plurality of markers 208 can be disposed in thefront distal section 259. The markers 208 can be sized and configured toaid in locating and identifying the orientation of the distal endsection 259. For example, the markers 208 can be located and/or viewedwith external ultrasonic imaging systems (not shown), such as thosecommonly used in similar medical procedures.

[0354] A further advantage is provided where the stent deliveryapplicator 201 is both steerable and configured for multiple stentimplantation. As such, the applicator 201 can be inserted into theanterior chamber 20, through an incision, such as a corneal incision,and multiple stents can then be implanted at different locations withoutremoving the applicator 201 or creating other incisions, described ingreater detail below.

[0355]FIG. 52A shows another embodiment of the stent delivery distalportion 241, identified generally by the reference numeral 241B, andanother embodiment of a stent, identified generally by the referencenumeral 229E.

[0356] The stent 229E comprises a first (proximal) flange 240E and asecond (distal) flange 237E with a plurality of supporting legs or posts236. The second flange 237E of the stent 229E is configured to befoldable. For example, the first flange 237E can be configured to beelastically foldable toward an upstream direction. As such, the firstflange 237E can be folded toward an upstream direction, as illustratedin FIG. 52A when stored in the sheath 246. Thus, after the first flange237E has been pushed through the end 242, the first flange 237E canresiliently unfold. As such, the first flange 237E can provide enhancedanchoring for the stent 229E when implanted into the trabecular meshwork21.

[0357] A further advantage can be provided where the applicator 201includes a cutting device that can extend through the lumens 239E of thestents 229E. For example, as shown in FIG. 52A, a cutting device 250 caninclude a cutting tip 247 and can be configured to extend through thestents 229E during an implantation procedure. As such, the cuttingdevice can being an incision at the center of the site at which thestent 229E is to be inserted through the trabecular meshwork 21. In theillustrated embodiment, the cutting device is in the form of a trocar.

[0358] With continued reference to FIG. 52A, the cutting device 250 isconfigured to be moveable axially through the lumen 249 of theapplicator end portion 241B of the sheath 146. Additionally, the cuttingdevice 250 can be moved axially relative to the stent or stents throughwhich it extends.

[0359] Another advantage can be provided where the cutting device 250also includes at least one holding member for holding a stent. Forexample, the cutting device 250 includes at least one holding device245, described above with reference to FIG. 51B, can be configured tohold a stent at least during an implantation procedure, and to releasethe stent at the appropriate time.

[0360] Preferably, the holding members 245B are arranged to align thesides of the cutting tip 247 with the distally facing sides of theflange 237E when the flange 237E is folded. For example, as shown inFIG. 52A, when the flange 237E is folded, the distally facing side ofthe flange 237E is aligned with the sides of the cutting tip 247, asindicated by the dashed-lines identified by the letter “A.” Thisalignment can be facilitated by arranging the holding members 245B suchthat the cutting device 250 extends distally from the flange 237Esufficiently to cause the sides of the cutting tip 247 to become alignedwith the flange 237E. As such, the sides of the cutting tip 247 and thedistally facing side of the flange 237E generate a more smooth surfacefor penetrating the trabecular meshwork 21 during an implantationprocedure.

[0361] During operation, the applicator end portion 241B can be pushedinto trabecular meshwork 21, with the flange 237E disposed in Schlemm'scanal 22, as shown in FIG. 52B. The sheath 246 can then be retracted outof Schlemm's canal 22, leaving the cutting device 250 and stent 229E inplace (FIG. 52C).

[0362] With the sheath 246 retracted, the first flange 237E can unfold,as indicated by the arrows U in FIG. 52C, thereby providing enhancedanchoring of the stent 229E within Schlemm's canal 22 (FIG. 52D).Additionally, the second flange 240E is within the anterior chamber 20.

[0363] As shown in FIG. 52D, the cutting device 250 can then beretracted relative to the applicator end portion 241B and the stent229E, leaving the stent 229E in place. Optionally, the cutting device250 and the sheath 246 can be retracted together.

[0364] As noted above, the holding members 245 are configured to limitthe movement of the stents 229E relative to the cutting device 250. Whenthe cutting device is retracted, the next stent 229E preferably is movedpassed (in the downstream direction) the holding member 245 that waspreviously between the stents 229E. As such, the next stent 229E can bemoved into position for implantation. Thus, the holding members 245preferably are configured to allow the stent 229E to move toward thecutting tip 247 when the cutting device 250 is retracted. For example,the holding members 245 can be controlled so as to retract when thecutting device 250 is retracted.

[0365] With reference to FIG. 53, another embodiment of an axisymmetrictrabecular stenting device is illustrated therein and identifiedgenerally by the reference numeral 229F. For ease of description, butwithout limitation, the stent 229F is described below with reference tocylindrical coordinates of x, r and angle α as shown in FIG. 53.

[0366] The stent 229F comprises an inlet (proximal) section having afirst flange 240F, an outlet (distal) section having a second flange237F and a middle section 284 connecting the inlet section and theoutlet section. A lumen 239F of the device 229F is configured totransport aqueous, liquid, or therapeutic agents between the inletsection and the outlet section. As referred to herein, “therapeuticagent” is intended to include pharmaceutical agents, drugs, genes,cells, proteins, and/or growth factors.

[0367] The inlet section of the stent 229F has at least one inletopening 286 and the outlet section comprises at least one outlet opening287. A further advantage is provided where the outlet section 237Fincludes at least one opening 287, 288 suitably located for dischargingsubstantially axisymmetrically the aqueous, liquid or therapeuticagents, wherein the opening 287, 288 is in fluid communication with thelumen 285 of the device 281. In the illustrated embodiment, the openings288 extend radially from the lumen 285 and open at the outwardly facingsurface around the periphery of the outlet flange 237F.

[0368] In one embodiment of an implantation procedure, Pilocarpine isadministered preoperatively to constrict the pupil to provide maximalprotection of the lens in phakic individuals and to further open theanterior chamber angle to provide a better view of the surgical site.Topical and retrobulbar anesthetic are recommended. A small self-sealingtemporal corneal incision can be made and Healon® viscoelastic (VE) canbe injected to maintain the anterior chamber.

[0369] A microscope can be tilted slightly toward the surgeon and thepatient's head can be rotated away from the surgeon to provide asuitable view of the nasal trabecular meshwork using a direct-viewgonioscope that is placed on the eye. The applicator 201 with apreloaded stent, such as, for example, but without limitation, an one orany combination of the stents a plurality of any combination of thestents 229, 30, 30 a, 30 b, 30 c, 30 d, 30 e, 30 f, 30 g, 30 h, 30 i, 30j, 30 k, 30 m, 30 n, 30 p, 30 q, 30 r, 30 s, 30 t, 30 u, 30 v, 229A,229B, 229C, 229D, 229E, 229F, or any of the other stents describedbelow, is advanced through the corneal wound and across the anteriorchamber. The stent is pushed against the trabecular meshwork and movedinferiorly to pierce the trabecular meshwork and guide the stent intoSchlemm's canal. After successful implantation and release of the stent,the applicator is withdrawn and the VE is flushed from the eye.

[0370] The G2 stent (for example, stent 229F of FIG. 53) can be smallerand of a significantly different design than the G1 stents, thusallowing it to be passed through a smaller corneal incision and beimplanted with a simple axial motion. Reduced size and simplifiedsurgical motions may enable implantation of the G2 stent without the useof viscoelastic and therefore eliminate a significant expendablematerial cost and the time necessary to administer and remove it.

[0371] Additionally, viscoelastic use in patients undergoing eye surgerycan cause post-operative transient IOP spikes that can further damagethe remaining glaucoma-compromised retina. Reduced surgicalmanipulations reduce the burden on the surgeon and reduce thestimulation and irritation of intraocular tissues. Furthermore,reduction in the corneal incision size raises the possibility that theincision could be made by the G2 applicator, and could potentiallyreduce the surgical implant procedure to an injectable implantprocedure. Injectable stent therapy represents a potentially superioralternative to both end-stage surgical therapy and to patients burdenedby the cumulative side effects, complications, and compliance issuesassociated with drug therapy.

[0372] The G2 stent and applicator system are sized, dimensioned andconfigured for placement through trabecular meshwork in an ab interno orab externo procedures. FIGS. 54A-C illustrate additional examples ofpreferred G2 stent and applicator embodiments.

[0373]FIG. 54A shows yet another embodiment of a stent injector assemblyfor multiple stent deployment, identified generally by the referencenumeral 260. The stent injector 260 comprises a housing 261 with adistal cap 262 and a distal stent-holding element 263 that is distalfrom the distal cap 261. Optionally, at least a portion of the distalstent-holding element 263 can be configured to be steerable with asteering mechanism that can be constructed in accordance with thedescription of the steerable section 251 described above with referenceto FIGS. 51A-D.

[0374] The stent-holding element 263 can comprise an elongate member 264with at least one stent slideably disposed thereon. The elongate member264 can be configured to extend through the lumen of any of the stents229A, 229B, 229C, 229D, 229E, 229F, or any of the other stents describedbelow.

[0375] In the illustrated embodiment, the elongate member 264 extendsthrough the lumen of stents 229G (FIG. 54B). In one embodiment, thedistal stent 229G can be the same as the second or proximal stent 229G.In another embodiment, the distal stent and the proximal stent aredifferent in size or configuration for placement at different locations.For example, the proximal and distal stents of FIG. 54B can be anycombination of the stents 229A, 229B, 229C, 229D, 229E, 229F, and 229G.Additionally, the applicator 260 can be configured to be loaded withonly one, three, or more stents.

[0376] In the illustrated embodiment, the distal flange 237G of thestent 229G can be wedge-shaped. For example, the distal end of theflange 237G can have a smaller diameter than that of the proximal end ofthe flange 237G. As such, the stent 229G can pass more easily throughthe trabecular meshwork 21. Additionally, the distally facing surface ofthe flange 237G can be inclined so as to be aligned with a distalsurface of the elongate member 264. As noted above with respect to thecutting member 250, the elongate member 264 can be in the form of atrocar.

[0377] The stent-holding element further comprises a sleeve 265configured to support the elongate member 264. The sleeve 265 (forexample, made of hypo tubing) can be pressed or bonded onto the distalcap 262 to form a sleeve-cap subassembly. The elongate member 264 can beconfigured to be axially moveable relative to the sleeve 265, asindicated by the arrow 266 (FIG. 54C).

[0378] The housing 261 can also comprise a tip actuator 267 that has adistal end 268 and a proximal end 269. The elongate member 264 can bepress fit or bonded into the distal end portion of the tip actuator 267to form a tip/tip actuator subassembly. In one exemplary butnon-limiting embodiment, the elongate member 264 can be a 0.08 mmdiameter sharpened rod made from a hard material, such as a metal.

[0379] The tip/tip actuator subassembly is fed through the sleeve-capsubassembly and the cap 262 is screwed onto or bonded with the housing261. The proximal end 269 can include a threaded portion 270 adapted forthreaded engagement with a rotation knob 271 located at the proximal endportion of the housing 261. Thus, the coupling mechanism comprises thetip/tip-actuator subassembly screwed into the rotation knob 271 to forman actuator-knob subassembly.

[0380] An interlock arrangement 272 is configured to retain the knob 271on the housing 261 and allow the knob 271 to rotate relative to thehousing 261. The interlock arrangement 272 can include an annular ribdisposed on the housing 261 and a groove disposed on the knob 271. Aclearance is provided between the groove and the rib so as to allow theknob 271 to rotate freely relative to the housing 261. The knob 271 canbe pressed onto the housing 261 and thus spins freely on housing 261without coming off because of an interlock arrangement 272.

[0381] With reference to FIGS. 54A and 54C, the housing 261 can includea slot line 273 at a location perpendicular to a longitudinal axis 275of the housing. One side of the slot line 273 can be drilled through tothe opposite side of the housing, thus allowing an anti-rotation pin 274to extend therethrough.

[0382]FIG. 54C shows a top cross-sectional view, identified as section3-3 of FIG. 54A, with the anti-rotation pin 274 aligned with the slot276. During assembly, of the injector 260, the tip actuator 267 isrotated until the slot 276 is aligned with the drilled hole adapted forthe anti-rotation pin 274 to extend into the drilled hole. Theanti-rotation pin 274 is pressed through a first side of housing,through the tip actuator, and through a second opposite side of housing.

[0383] In operation, one or more stents are placed over the member 264and against the blunt front end of the sleeve 265. After the injectorapproaches the target site, the elongate member 264 and the first stentare pressed into tissue where implantation is to take place. In an abinterno procedure, the first tissue is the trabecular meshwork facingthe anterior chamber. In an ab externo procedure, the first tissue isthe trabecular meshwork facing Schlemm's canal. Once the first stent isin a proper location, the knob 271 is rotated to withdraw the elongatemember 264, leaving the first stent in place. Stents can be snugly heldonto the tip 264 with a mechanical feature on the elongate member, suchas the holding members 245 described above with reference to FIGS.51A-D. Optionally, the sleeve 265 can include a mechanical feature forholding stents in place. Further viscoelastic material or other meanscan be provided for holding the stents so that stent deployment does notoccur until desired.

[0384]FIG. 55 shows an embodiment of the seton implant 331 constructedaccording to the principles of the invention. The seton implant maycomprise a biocompatible material, such as a medical grade silicone, forexample, the material sold under the trademark Silastic™, which isavailable from Dow Corning Corporation of Midland, Mich., orpolyurethane, which is sold under the trademark Pellethane™, which isalso available from Dow Corning Corporation. In an alternate embodiment,other biocompatible materials (biomaterials) may be used, such aspolyvinyl alcohol, polyvinyl pyrolidone, collagen, heparinized collagen,tetrafluoroethylene, fluorinated polymer, fluorinated elastomer,flexible fused silica, polyolefin, polyester, polysilicon, mixture ofbiocompatible materials, and the like. In a further alternateembodiment, a composite biocompatible material by surface coating theabove-mentioned biomaterial may be used, wherein the coating materialmay be selected from the group consisting of polytetrafluoroethylene(PTFE), polyimide, hydrogel, heparin, therapeutic drugs, and the like.

[0385] The main purpose of the seton implant is to assist infacilitating the outflow of aqueous in an outward direction 340 into theSchlemm's canal and subsequently into the aqueous collectors and theaqueous veins so that the intraocular pressure is balanced. In oneembodiment, the seton implant 331 comprises an elongated tubular elementhaving a distal section 332 and an inlet section 344. A rigid orflexible distal section 332 is positioned inside one of the existingoutflow pathways. The distal section may have either a tapered outletend 333 or have at least one ridge 337 or other retention deviceprotruding radially outwardly for stabilizing the seton implant insidethe existing outflow pathways after implantation. For stabilizationpurposes, the outer surface of the distal section 332 may comprise astubbed surface, a ribbed surface, a surface with pillars, a texturedsurface, or the like. The outer surface 336, including the outer region335 and inner region 334 at the outlet end 333, of the seton implant isbiocompatible and tissue compatible so that the interaction/irritationbetween the outer surface and the surrounding tissue is minimized. Theseton implant may comprise at least one opening at a location proximalthe distal section 332, away from the outlet end 333, to allow flow ofaqueous in more than one direction. The at least one opening may belocated on the distal section 332 at about opposite of the outlet end333.

[0386] In another exemplary embodiment, the seton implant 331 may have aone-way flow controlling means 339 for allowing one-way aqueous flow340. The one-way flow controlling means 339 may be selected from thegroup consisting of a check valve, a slit valve, a micropump, asemi-permeable membrane, or the like. To enhance the outflow efficiency,at least one optional opening 341 in the proximal portion of the distalsection 332, at a location away from the outlet end 333, and in anexemplary embodiment at the opposite end of the outlet end 333, isprovided.

[0387]FIG. 56 shows a top cross-sectional view of FIG. 55. The shape ofthe opening of the outlet end 333 and the remaining body of the distalsection 332 may be oval, round or some other shape adapted to conform tothe shape of the existing outflow pathways. This configuration willmatch the contour of Schlemm's canal to stabilize the inlet section withrespect to the iris and cornea by preventing rotation.

[0388] As shown in FIG. 55, the seton implant of the present inventionmay have a length between about 0.5 mm to over a meter, depending on thebody cavity the seton implant applies to. The outside diameter of theseton implant may range from about 30 μm to about 500 μm. The lumendiameter is preferably in the range between about 20 μm to about 150 μm.The seton implant may have a plurality of lumens to facilitate multipleflow transportation. The distal section may be curved at an anglebetween about 30 degrees to about 150 degrees, in an exemplaryembodiment at around 70-110 degrees, with reference to the inlet section344.

[0389]FIG. 57 shows another embodiment of the seton implant 345constructed in accordance with the principles of the invention. In anexemplary embodiment, the seton implant 345 may comprise at least twosections: an inlet section 347 and an outlet section 346. The outletsection has an outlet opening 48 that is at the outlet end of the setonimplant 345. The shape of the outlet opening 348 is preferably an ovalshape to conform to the contour of the existing outflow pathways. Aportion of the inlet section 347 adjacent the joint region to the outletsection 346 will be positioned essentially through the diseasedtrabecular meshwork while the remainder of the inlet section 347 and theoutlet section 346 are outside the trabecular meshwork. As shown in FIG.5, the long axis of the oval shape opening 348 lies in a first planeformed by an X-axis and a Y-axis. To better conform to the anatomicalcontour of the anterior chamber 20, the trabecular meshwork 21 and theexisting outflow pathways, the inlet section 347 may preferably lie atan elevated second plane, at an angle θ, from the first plane formed byan imaginary inlet section 347A and the outlet section 346. The angle θmay be between about 30 degrees and about 150 degrees.

[0390] After the first stent is implanted, the injector is slightlywithdrawn away from the trabecular meshwork. The tip of the injector ismoved and pointed to a second target site without withdrawing theinjector from the incision on the sclera. This re-positioning of theinjector can be accomplished with a steerable section of the injector260 noted above.

[0391] The term “targeted placement” of trabecular stents refers to theintentional placement of a stent at a particular location in Schlemm'scanal for the purpose of providing a maximum benefit in the form ofmaximum outflow facility. With reference to FIG. 50A, aqueous entersSchlemm's canal 22 through the trabecular meshwork 21 and travels alongthe canal to exit through the collector channels 23. Schlemm's canal isa narrow channel with approximate dimensions of 250 μm x 201 μm with a40 mm length (Volume ˜0.2 μl) and it provides measurable resistance tothe flow of aqueous. Therefore, placing a stent into Schlemm's canal 22through the trabecular meshwork 21 yields the best improvement inoutflow facility when it is placed near a large collector channel 23 ora group of smaller ones that combine to have a larger hydraulicdiameter. It is one aspect of the present invention to locate/detect themost appropriate collector channel(s) to implant a trabecular shuntingstent adjacent the collector channel(s) 23.

[0392] The term “Multi-stent therapy” refers to the intentionalplacement of a stent in each of several locations in Schlemm's canal 22.Since Schlemm's canal 22 has measurable resistance to flow atphysiological flow rates, a plurality of stents is strategically placedclose to concentrations of collector ducts 23 or a large collector anddistributed around Schlemm's canal 22 to maximize the impact of multiplestents.

[0393] An injector or device applicator to hold a plurality of serialdevices has advantages of placing the device one at a time withoutreloading the device or without completely withdrawing the applicatorout of a portion of the body. The advantages may include savingoperating time, reducing redundant incision or injury, or exactpositioning for device placement.

[0394] By way of example, but without limitation, an injector or deviceapplicator for multiple device deployment may be used for implantingpunctum plugs in an eye, for implanting drug-eluting devices into scleratissue of an eye, implanting drug-eluting devices into tissue of aposterior segment, or implanting cardiovascular stents. Some aspects ofat least one of the inventions disclosed herein relate to a method ofmultiple device deployment comprising: (a) loading a plurality ofdevices within a device-retaining space of a device applicator; (b)delivering the applicator to a first target implant site; (c) deployinga first device at the first target implant site; (d) detaching theapplicator from the first target implant site; (e) directing theapplicator to a second target implant site; (f) deploying a seconddevice at the second target implant site; and (g) withdrawing theapplicator.

[0395] The device of the exemplary embodiment preferably comprises abiocompatible material such that inflammation arising due to irritationbetween the outer surface of the device and the surrounding tissue isminimized. Biocompatible materials which may be used for the device 81preferably include, but are not limited to, titanium, titanium alloys,polypropylene, nylon, PMMA (polymethyl methacrylate), medical gradesilicone, e.g., Silastic™, available from Dow Corning Corporation ofMidland, Mich.; and polyurethane, e.g., Pellethane™, also available fromDow Corning Corporation.

[0396] In other embodiments, the device of the embodiments may compriseother types of biocompatible material, such as, by way of example,polyvinyl alcohol, polyvinyl pyrolidone, collagen, heparinized collagen,polytetrafluoroethylene, expanded polytetrafluoroethylene, fluorinatedpolymer, fluorinated elastomer, flexible fused silica, polyolefin,polyester, polysilicon, and/or a mixture of the aforementionedbiocompatible materials, and the like. In still other embodiments,composite biocompatible material may be used, wherein a surface materialmay be used in addition to one or more of the aforementioned materials.For example, such a surface material may include polytetrafluoroethylene(PTFE) (such as Teflon™), polyimide, hydrogel, heparin, therapeuticdrugs (such as beta-adrenergic antagonists and other anti-glaucomadrugs, or antibiotics), and the like.

[0397]FIG. 58 illustrates a preferred embodiment of a trabecularshunting/stenting device 431, which facilitates the outflow of aqueousfrom the anterior chamber 20 into Schlemm's canal 22, and subsequentlyinto the aqueous collectors and the aqueous veins so that intraocularpressure is reduced. In the illustrated embodiment, the trabecularstenting device 431 comprises an inlet section 402, having an inletopening 403, a middle section 404, and an outlet section 409. The middlesection 404 may be an extension of, or may be coextensive with, theinlet section 402. The outlet section 409 is preferably somewhatflexible to facilitate positioning of the outlet section 409 within anoutflow pathway of the eye 10. The outlet section 409 is preferablysubstantially perpendicular to the middle section 404. “Substantiallyperpendicular,” as used herein, is defined as subtending an anglebetween longitudinal axes of the sections 404, 409 ranging between about30 degrees and about 150 degrees. The device 431 further comprises atleast one lumen 407 within sections 404 and 409 which is in fluidcommunication with the inlet opening 403 of section 402, therebyfacilitating transfer of aqueous through the device 431.

[0398] In one embodiment, the outlet section 409 has at least one outletend. In another embodiment, the outlet section preferably has a firstoutlet end 406 and a second, opposite outlet end 405. The lumen 407within the outlet section 409 opens to at least one of the outlet ends405, 406. Furthermore, the outlet section 409 may have a plurality ofside openings 477, each of which is in fluid communication with thelumen 407, for transmission of aqueous. The middle section 404 isconnected to or coextensive with the outlet section 409 and is disposedbetween the first outlet end 406 and the second outlet end 405. In apreferred embodiment, the outlet section 409 is curved around a point,or a curve center, and the middle section 404 extends substantiallyalong a plane that contains the curve center. In this embodiment, theoutlet section 409 has a radius of curvature ranging between about 4 mmand about 10 mm.

[0399] As will be apparent to a person skilled in the art, the lumen 407and the remaining body of the outlet section 409 may have across-sectional shape that is oval, circular, or other appropriateshape. The cross-sectional shapes of the lumen 407 and the outletsection 409 preferably conform to the shape of the outflow pathway intowhich the outlet section 409 is placed. The opening of the lumen 407 ofthe outlet ends 405, 406 may be ovoid in shape to match the contour ofSchlemm's canal 22. Further, an outer contour of the outlet section 409may be elliptical (e.g., ovoid) in shape to match the contour ofSchlemm's canal 22. This serves to minimize rotational movement of theoutlet section 409 within Schlemm's canal 22, and thereby stabilizes theinlet section 402 with respect to the iris and cornea.

[0400] A circumferential ridge 408 is provided at the junction of theinlet section 402 and the middle section 404 to facilitate stabilizationof the device 431 once implanted within the eye 10. Preferably, themiddle section 404 has a length (between the ridge 408 and the outletsection 409) that is roughly equal to a thickness of the trabecularmeshwork 21, which typically ranges between about 100 μm and about 300μm. In addition, the outlet section 409 may advantageously be formedwith a protuberance or spur projecting therefrom so as to furtherstabilize the device 431 within the eye 10 without undue suturing.

[0401]FIG. 63 is a close-up view of the inlet section 402 of thetrabecular stenting device 431, illustrating a flow-restricting member472, which is tightly retained within a lumen 478. The flow-restrictingmember 472 is shown located close to an inlet side 471 of the inletsection 402. The flow-restricting member 472 serves to selectivelyrestrict at least one component in blood from moving retrograde, i.e.,from the outlet section 409 into the anterior chamber 20 of the eye 10.Alternatively, the flow-restricting member 472 may be situated in anylocation within the device 431 such that blood flow is restricted fromretrograde motion. The flow-restricting member 472 may, in otherembodiments, be a filter made of a material selected from the followingfilter materials: expanded polytetrafluoroethylene, cellulose, ceramic,glass, Nylon, plastic, and fluorinated material such as polyvinylidenefluoride (“PVDF”) (trade name: Kynar, by DuPont).

[0402] The trabecular stenting device 431 may be made by molding,thermo-forming, or other micro-machining techniques. The trabecularstenting device 431 preferably comprises a biocompatible material suchthat inflammation arising due to irritation between the outer surface ofthe device 431 and the surrounding tissue is minimized. Biocompatiblematerials which may be used for the device 431 preferably include, butare not limited to, titanium, medical grade silicone, e.g., Silastic™,available from Dow Corning Corporation of Midland, Mich.; andpolyurethane, e.g., Pellethane™, also available from Dow CorningCorporation. In other embodiments, the device 431 may comprise othertypes of biocompatible material, such as, by way of example, polyvinylalcohol, polyvinyl pyrolidone, collagen, heparinized collagen,polytetrafluordethylene, expanded polytetrafluoroethylene, fluorinatedpolymer, fluorinated elastomer, flexible fused silica, polyolefin,polyester, polysilicon, and/or a mixture of the aforementionedbiocompatible materials, and the like. In still other embodiments,composite biocompatible material may be used, wherein a surface materialmay be used in addition to one or more of the aforementioned materials.For example, such a surface material may include polytetrafluoroethylene(PTFE) (such as Teflon™), polyimide, hydrogel, heparin, therapeuticdrugs (such as beta-adrenergic antagonists and other anti-glaucomadrugs, or antibiotics), and the like.

[0403] As is well known in the art, a device coated or loaded with aslow-release substance can have prolonged effects on local tissuesurrounding the device. The slow-release delivery can be designed suchthat an effective amount of substance is released over a desiredduration. “Substance,” as used herein, is defined as any therapeutic orbioactive drug or agents that can stop, mitigate, slow-down or reverseundesired disease processes.

[0404] In one embodiment, the device 431 may be made of a biodegradable(also including bioerodible) material admixed with a substance forsubstance slow-release into ocular tissues. In another embodiment,polymer films may function as substance containing release deviceswhereby the polymer films may be coupled or secured to the device 431.The polymer films may be designed to permit the controlled release ofthe substance at a chosen rate and for a selected duration, which mayalso be episodic or periodic. Such polymer films may be synthesized suchthat the substance is bound to the surface or resides within a pore inthe film so that the substance is relatively protected from enzymaticattack. The polymer films may also be modified to alter theirhydrophilicity, hydrophobicity and vulnerability to platelet adhesionand enzymatic attack. In one embodiment, the polymer film is made ofbiodegradable material.

[0405] Furthermore, the film may be coupled (locally or remotely) to apower source such that when substance delivery is desired, a brief pulseof current is provided to alter the potential on the film to cause therelease of a particular amount of the substance for a chosen duration.Application of current causes release of a substance from the surface ofthe film or from an interior location in the film such as within a pore.The rate of substance delivery is altered depending on the degree ofsubstance loading on the film, the voltage applied to the film, and bymodifying the chemical synthesis of substance delivery polymer film.

[0406] The power-activated substance delivery polymer film may bedesigned to be activated by an electromagnetic field, such as, by way ofexample, NMR, MRI, or short range RF transmission (such as a Bluetooth®apparatus). In addition, ultrasound can be used to cause a release of aparticular amount of substance for a chosen duration. This isparticularly applicable to a substance coated device or a device made ofa substrate containing the desired substance.

[0407] The device 431 may be used for a direct release of pharmaceuticalpreparations into ocular tissues. As discussed above, thepharmaceuticals may be compounded within the device 431 or form acoating on the device 431. Any known drug therapy for glaucoma may beutilized, including but not limited to, the following:

[0408] U.S. Pat. No. 6,274,138, issued Aug. 14, 2001, and U.S. Pat. No.6,231,853, issued May 15, 2001, the entire contents of both of which areincorporated herein by reference, disclose the function of mitochondriaand toxic substances synthesized as a metabolic byproduct withinmitochondria of cells. Perry and associates (Perry HD et al. “Topicalcyclosporin A in the management of postkeratoplasty glaucoma” Cornea16:284-288, 1997) report that topical cyclosporin-A has been shown toreduce post-surgical increases in intraocular pressure. It is proposedthat such compounds with known effects on mitochondrial stability mightbe effective in treating trabecular meshwork. An antagonistic drug toneutralize the toxic byproduct or a stabilizing drug to effectmitochondrial stability is believed able to restore the mitochondriafunction and subsequently mitigate the dysfunction of the trabecularmeshwork.

[0409] U.S. Pat. No. 6,201,001, issued Mar. 13, 2001, the entirecontents of which are incorporated herein by reference, disclosesImidazole antiproliferative agents useful for neovascular glaucoma.

[0410] U.S. Pat. No. 6,228,873, issued May 8, 2001, the entire contentsof which are incorporated herein by reference, discloses a new class ofcompounds that inhibit function of sodium chloride transport in thethick ascending limb of the loop of Henle, wherein the preferredcompounds useful are furosemide, piretanide, benzmetanide, bumetanide,torasernide and derivatives thereof.

[0411] U.S. Pat. No. 6,194,415, issued Feb. 27, 2001, the entirecontents of which are incorporated herein by reference, discloses amethod of using quinoxalines (2-imidazolin-2-ylamino) in treating neuralinjuries (e.g., glaucomatous nerve damage).

[0412] U.S. Pat. No. 6,060,463, issued May 9, 2000, and U.S. Pat. No.5,869,468, issued Feb. 9, 1999, the entire contents of which areincorporated herein by reference, disclose treatment of conditions ofabnormally increased intraocular pressure by administration ofphosphonylmethoxyalkyl nucleotide analogs and related nucleotideanalogs.

[0413] U.S. Pat. No. 5,925,342, issued Jul. 20, 1999, the entirecontents of which are incorporated herein by reference, discloses amethod for reducing intraocular pressure by administration of potassiumchannel blockers.

[0414] U.S. Pat. No. 5,814,620, issued Sep. 29, 1998, the entirecontents of which are incorporated herein by reference, discloses amethod of reducing neovascularization and of treating various disordersassociated with neovascularization. These methods include administeringto a tissue or subject a synthetic oligonucleotide.

[0415] U.S. Pat. No. 5,767,079, issued Jun. 16, 1998, the entirecontents of which are incorporated herein by reference, discloses amethod for treatment of ophthalmic disorders by applying an effectiveamount of Transforming Growth Factor-Beta (TGF-beta) to the affectedregion.

[0416] U.S. Pat. No. 5,663,205, issued Sep. 2, 1997, the entire contentsof which are incorporated herein by reference, discloses apharmaceutical composition for use in glaucoma treatment which containsan active ingredient5-[1-hydroxy-2-[2-(2-methoxyphenoxyl)ethylamino]ethyl]-2-methylbenzenesulfonamide.This agent is free from side effects, and stable and has an excellentintraocular pressure reducing activity at its low concentrations, thusbeing useful as a pharmaceutical composition for use in glaucomatreatment.

[0417] U.S. Pat. No. 5,652,236, issued Jul. 29, 1997, the entirecontents of which are incorporated herein by reference, disclosespharmaceutical compositions and a method for treating glaucoma and/orocular hypertension in the mammalian eye by administering thereto apharmaceutical composition which contains as the active ingredient oneor more compounds having guanylate cyclase inhibition activity. Examplesof guanylate cyclase inhibitors utilized in the pharmaceuticalcomposition and method of treatment are methylene blue, butylatedhydroxyanisole and N-methylhydroxylamine.

[0418] U.S. Pat. No. 5,547,993, issued Aug. 20, 1996, the entirecontents of which are incorporated herein by reference, discloses that2-(4methylaminobutoxy) diphenylmethane or a hydrate or pharmaceuticallyacceptable salt thereof have been found useful for treating glaucoma.

[0419] U.S. Pat. No. 5,502,052, issued Mar. 26, 1996, the entirecontents of which are incorporated herein by reference, discloses use ofa combination of apraclonidine and timolol to control intraocularpressure. The compositions contain a combination of an alpha-2 agonist(e.g., para-amino clonidine) and a beta blocker (e.g., betaxolol).

[0420] U.S. Pat. No. 6,184,250, issued Feb. 6, 2001, the entire contentsof which are incorporated herein by reference, discloses use ofcloprostenol and fluprostenol analogues to treat glaucoma and ocularhypertension. The method comprises topically administering to anaffected eye a composition comprising a therapeutically effective amountof a combination of a first compound selected from the group consistingof beta-blockers, carbonic anhydrase inhibitors, adrenergic agonists,and cholinergic agonists, together with a second compound.

[0421] U.S. Pat. No. 6,159,458, issued Dec. 12, 2000, the entirecontents of which are incorporated herein by reference, discloses anophthalmic composition that provides sustained release of a watersoluble medicament formed by comprising a crosslinked carboxy-containingpolymer, a medicament, a sugar and water.

[0422] U.S. Pat. No. 6,110,912, issued Aug. 29, 2000, the entirecontents of which are incorporated herein by reference, disclosesmethods for the treatment of glaucoma by administering an ophthalmicpreparation comprising an effective amount of a non-corneotoxicserine-threonine kinase inhibitor, thereby enhancing aqueous outflow inthe eye and treatment of the glaucoma. In some embodiments, the methodof administration is topical, whereas it is intracameral in otherembodiments. In still further embodiments, the method of administrationis intracanalicular.

[0423] U.S. Pat. No. 6,177,427, issued Jan. 23, 2001, the entirecontents of which are incorporated herein by reference, disclosescompositions of non-steroidal glucocorticoid antagonists for treatingglaucoma or ocular hypertension.

[0424] U.S. Pat. No. 5,952,378, issued Sep. 14, 1999, the entirecontents of which are incorporated herein by reference, discloses theuse of prostaglandins for enhancing the delivery of drugs through theuveoscleral route to the optic nerve head for treatment of glaucoma orother diseases of the optic nerve as well as surrounding tissue. Themethod for enhancing the delivery to the optic nerve head comprisescontacting a therapeutically effective amount of a compositioncontaining one or more prostaglandins and one or more drug substanceswith the eye at certain intervals.

[0425]FIG. 59 illustrates another embodiment of a trabecular stentingdevice 431A that facilitates the outflow of aqueous from the anteriorchamber 20 into Schlemm's canal 22, and subsequently into the aqueouscollectors and the aqueous veins so that intraocular pressure isreduced. The device 431A comprises an inlet section 402A, a middlesection 404A, and an outlet section 409A. The device 431A furthercomprises at least one lumen 403A traversing the sections 402A, 404A,409A and providing fluid communication therebetween. The lumen 403Afacilitates the transfer of aqueous from the inlet section 402A throughthe device 431A. The outlet section 409A is preferably curved, and mayalso be somewhat flexible, to facilitate positioning of the outletsection 409A within an existing outflow pathway of the eye 10. Theoutlet section 409A may further comprise an elongate trough 7A fortransmitting, or venting, aqueous. The elongate trough 7A is connectedto and in fluid communication with the lumen 403A within the trabecularstenting device 431A.

[0426] A circumferential ridge 8A is provided at the junction of theinlet section 402A and the middle section 404A to facilitatestabilization of the device 431A once implanted within the eye 10.Preferably, the middle section 404A has a length (between the ridge 8Aand the outlet section 409A) that is roughly equal to the thickness ofthe trabecular meshwork 21, which typically ranges between about 100 μmand about 300 μm. In addition, the outlet section 409A mayadvantageously be formed with a protuberance or barb projectingtherefrom so as to further stabilize the device 431A within the eye 10without undue suturing.

[0427] As will be appreciated by those of ordinary skill in the art, thedevices 431 and 431A may advantageously be practiced with a variety ofsizes and shapes without departing from the scope of the invention.Depending upon the distance between the anterior chamber 20 and thedrainage vessel (e.g., a vein) contemplated, the devices 431, 431A mayhave a length ranging from about 0.05 centimeters to over 10centimeters. Preferably, the devices 431 and 431A have an outsidediameter ranging between about 30 μm and about 500 μm, with the lumens407, 403A having diameters ranging between about 20 μm and about 250 μm,respectively. In addition, the devices 431, 431A may have a plurality oflumens to facilitate transmission of multiple flows of aqueous. Theinlet sections 402, 402A have longitudinal axes that form an angle (θ)ranging between about 20 degrees and about 150 degrees relative to thelongitudinal axes of the middle sections 404, 404A, respectively. Morepreferably, the angles between the longitudinal axes of the inletsections 402, 402A and the middle sections 404, 404A range between about30 degrees and about 60 degrees, respectively.

[0428] One preferred method for increasing aqueous outflow in the eye 10of a patient, to reduce intraocular pressure therein, comprisesbypassing the trabecular meshwork 21. In operation, the middle section404 of the device 431 is advantageously placed across the trabecularmeshwork 21 through a slit or opening. This opening can be created byuse of a laser, a knife, or other surgical cutting instrument. Theopening may advantageously be substantially horizontal, i.e., extendinglongitudinally in the same direction as the circumference of the limbus15. Other opening directions may also be used, as well. The opening mayadvantageously be oriented at any angle, relative to the circumferenceof the limbus 15, that is appropriate for inserting the device 431through the trabecular meshwork 21 and into Schlemm's canal 22 or otheroutflow pathway, as will be apparent to those skilled in the art. Themiddle section 404 may be semi-flexible and/or adjustable in positionrelative to the inlet section 402 and/or the outlet section 409, furtheradapting the device 431 for simple and safe glaucoma implantation.Furthermore, the outlet section 409 may be positioned into fluidcollection channels of the natural outflow pathways. Such naturaloutflow pathways include Schlemm's canal 22, aqueous collector channels,aqueous veins, and episcleral veins. The outlet section 409 may bepositioned into fluid collection channels up to at least the level ofthe aqueous veins, with the device inserted in a retrograde or antegradefashion.

[0429]FIG. 60 generally illustrates a step in the implantation of thetrabecular stenting device 431 through the trabecular meshwork 21. Theoutlet section 409 of the device 431 is inserted into an opening 61 inthe trabecular meshwork 21. A practitioner may create the opening 61 “abinterno” from the interior surface 65 of the trabecular meshwork 21. Thepractitioner then advances the first outlet end 406 of the outletsection 409 through the opening 61 into a first side of Schlemm's canal22 or other suitable outflow pathway within the eye 10. Next, thepractitioner advances the second outlet end 405 through the opening 61and into a second side of Schlemm's canal 22. The advancing of thesecond outlet end 405 may be facilitated by slightly pushing the secondoutlet end 405 through the opening 61.

[0430]FIG. 62 generally illustrates a further stage in deployment of thedevice 31, wherein the entire outlet section 409 of the device 431 isimplanted within Schlemm's canal 22, beneath the trabecular meshwork 21.At this stage, the lumen 403 of the implanted device 431 provides anenhanced fluid communication through the trabecular meshwork 21.

[0431]FIG. 61 shows an additional and/or alternate step in theimplantation of the trabecular stenting device 431 through thetrabecular meshwork 21. The practitioner inserts a distal end 463 of aguidewire 464 through the opening 61 into the first side of Schlemm'scanal 22. The practitioner then advances the first outlet end 406 of theoutlet section 409 into Schlemm's canal 22 by “riding,” or advancing,the trabecular stenting device 431 on the guidewire 464. As will beapparent to those skilled in the art, the guidewire 464 will have ashape and size conforming to the shape and size of the lumen 7; and assuch, may have an elliptical (e.g., oval) shape, a D-shape, a roundshape, or an irregular (asymmetric) shape which is adapted fornonrotatory engagement for the device 31.

[0432] Another method for increasing aqueous outflow within the eye 10of a patient, and thus reduce intraocular pressure therein, comprises:(a) creating an opening in the trabecular meshwork 21, wherein thetrabecular meshwork 21 includes a deep side and superficial side; (b)inserting the trabecular stenting device 431 into the opening; and (c)transmitting aqueous through the device 31, to bypass the trabecularmeshwork 21, from the deep side to the superficial side of thetrabecular meshwork 21. This “transmitting” of aqueous is preferablypassive, i.e., aqueous flows out of the anterior chamber 20 due to apressure gradient between the anterior chamber 20 and the aqueous venoussystem 23.

[0433] Another method for increasing aqueous outflow within the eye 10of a patient, and thus reduce intraocular pressure therein, comprises a)providing at least one bioactive substance incorporated into atrabecular stenting device at about the middle section of the device; b)implanting the trabecular stenting device within a trabecular meshworkof an eye such that the middle section is configured substantiallywithin the trabecular meshwork, the stenting device having a first endpositioned in an anterior chamber of the eye while a second end ispositioned inside a Schlemm's canal, wherein the first and the secondends of the trabecular stenting device establish a fluid communicationbetween the anterior chamber and the Schlemm's canal; and c) allowingthe middle section of the trabecular stenting device to release aquantity of the bioactive substance into the trabecular meshwork. Inanother embodiment, the at least one bioactive substance or agent isincorporated into the device at about the outlet section for releasingthe bioactive agent into Schlemm's canal and/or downstream of Schlemm'scanal.

[0434] It should be understood that the devices 431 and 31A are in nowway limited to implantation within only Schlemm's canal 20, as depictedin FIGS. 60 and 61. Rather, the devices 31 and 431A may advantageouslybe implanted within and/or used in conjunction with a variety of othernatural outflow pathways, or biological tubular structures, as mentionedabove. As will be apparent to those of ordinary skill in the art, thedevices 431 and 431A may advantageously be used in conjunction withsubstantially any biological tubular structure without detracting fromthe scope of the invention.

[0435]FIG. 64 shows one embodiment of an axisymmetric trabecularstenting device 481 according to the principles of the invention. Anaxisymmetric device 481 has a coordination of x, r and angle α as shownin FIG. 64, rather than depending on a conventional coordination of x,y, and z. The device 481 comprises an inlet (proximal) section 482, anoutlet (distal) section 483 and a middle section 484 connecting theinlet section 482 and the outlet section 483. A lumen 485 of the device481 is for transporting aqueous, liquid, or therapeutic agents betweenthe inlet section and the outlet section, wherein the therapeutic agentis herein intended to include pharmaceutical agents, drugs, genes,cells, and/or growth factors. The inlet section 482 has at least oneinlet opening 486 while the outlet section 483 comprises at least oneoutlet opening 487. In some aspect, the outlet section 483 may comprisea plurality of openings 487, 488 suitably located for outlettingaxisymmetrically the aqueous, liquid or therapeutic agents, wherein eachof the openings 488 is in fluid communication with the lumen 485 of thedevice 481.

[0436] In one embodiment, at least one bioactive agent is loaded ontothe exterior surface or into the pores of the exterior surface of themiddle section 404, 484 of the stenting device 431, 481 enablingreleasing into the trabecular meshwork upon device implantation. Ingeneral, the bioactive agents may comprise pharmaceutical agents, drugs,genes, cells, and/or growth factors. In some aspect, at least somebioactive agents may be loaded onto the inner surface or into the poresof the inner surface of the middle section of the stenting devices. Instill a further aspect, the middle section 404, 484 may be constructedof porous material enabling the loaded therapeutic agents controllablyreleasing to the desired surrounding tissue, wherein the therapeuticagents are diffusible through the pores. Preferably, the middle section484 has a length (between the inlet section 482 and the outlet section483) that is roughly equal to a thickness of the trabecular meshwork 21,which typically ranges between about 100 μm and about 300 μm.

[0437] Some aspects of the invention provide a stent with at least onebioactive agent being loaded onto the exterior surface or into the poresof the exterior surface of the outlet section 409, 483 of the stentingdevice 431, 481 enabling releasing into Schlemm's canal or collectorchannels upon device implantation.

[0438] To further stenting Schlemm's canal after implanting the device481, a plurality of elevated (that is, protruding axially) supports orpillars 489 is located at the distal-most end of the outlet section 483sized and configured for allowing media (for example, aqueous, liquid,balanced salt solution, viscoelastic fluid, therapeutic agents, or thelike) to be transported freely. Some aspects of the invention relate tothe device 481 having a plurality of elevated (that is, protrudingaxially) supports or pillars 489 that are made of biodegradable materialmixed with at least one bioactive agent. Once implanted, the bioactiveagent is slowly released from the biodegradable supports 489 to treatthe Schlemm's canal tissue.

[0439] In a further aspect, a plurality of the stenting device 481 isloaded in a cartridge to be inserted into a loading chamber of a devicedelivery applicator 451 or directly loaded inside the loading chamber ofa device delivery applicator 451 enabling for multiple stentsimplantation. In this method, the distal end of the applicator 451 ismovably positioned from one location at the trabecular meshwork afterimplanting a first stent to another location of the trabecular meshworkfor implanting a second stent and so forth without withdrawing theapplicator out of the anterior chamber of the eye.

[0440] Some aspects of the invention provide the device 431, 481 adaptedfor a direct release of at least one bioactive agent for treating oculartissues. As discussed above, the bioactive or therapeutic agents may becompounded within the device 431, 481 or form a coating on the device431, 481. Any known drug or non-drug therapeutic agents for glaucoma maybe utilized, including but not limited to, the following:

[0441] U.S. Pat. No. 6,436,703, issued Aug. 20, 2002, the entirecontents of which are incorporated herein by reference, discloses amethod and compositions comprising novel isolated polypeptides, novelisolated polynucleotides encoding such polypeptides, includingrecombinant DNA molecules, cloned genes or degenerate variants thereof,especially naturally occurring variants such as allelic variants,antisense polynucleotide molecules, and antibodies that specificallyrecognize one or more epitopes present on such polypeptides, as well ashybridomas producing such antibodies. The compositions in '703additionally include vectors, including expression vectors, containingthe polynucleotides of the invention, cells genetically engineered tocontain such polynucleotides and cells genetically engineered to expresssuch polynucleotides, any of which might be effective in treatingtrabecular meshwork and/or ocular tissue in general;

[0442] U.S. Pat. No. 6,423,682, issued Jul. 23, 2002 and U.S. Pat. No.6,485,920, issued Nov. 26, 2002, the entire contents of both of whichare incorporated herein by reference, disclose the compositions of novelhuman growth factor antagonist proteins and active variants thereof,isolated polynucleotides encoding such polypeptides, includingrecombinant DNA molecules, cloned genes or degenerate variants thereof,especially naturally occurring variants such as allelic variants,antisense polynucleotide molecules, and antibodies that specificallyrecognize one or more epitopes present on such polypeptides, as well ashybridomas producing such antibodies function of mitochondria and toxicsubstances synthesized as a metabolic byproduct within mitochondria ofcells. It is proposed that such compositions with known effects onmitochondrial stability might be effective in treating trabecularmeshwork. An antagonistic drug to neutralize the toxic byproduct or astabilizing drug to effect mitochondrial stability is believed able torestore the mitochondria function and subsequently mitigate thedysfunction of the trabecular meshwork;

[0443] U.S. Pat. No. 6,379,882, issued Apr. 30, 2002, the entirecontents of which are incorporated herein by reference, discloses amethod for reducing cellular damage related to myocardial infarction,glaucoma or another neurodegenerative disease by administering to asubject, a therapeutically effective amount of a test compound asdetermined by the relative efficacy of the test compound in reducingcell death due to the ischemic condition in an in vitro assay of growthfactor or oxygen/glucose and growth factor-deprived retinal ganglioncells. In the present invention, the in vitro cell death of growthfactor or oxygen/glucose and growth factor-deprived retinal ganglioncells generally occurs by an apoptotic or necrotic mechanism, whereinthe test compound comprises a calcium channel blocker, anN-methyl-D-aspartate, and a bis-benzimidazole;

[0444] U.S. Pat. No. 6,489,305, issued Dec. 3, 2002, the entire contentsof which are incorporated herein by reference, discloses a method forinhibiting proliferation of ocular fibroblasts or for amelioratingglaucoma surgery failure in a mammal, the method comprisingadministering to an eye of the mammal during or after glaucoma surgery ap21 cyclin dependent kinase inhibitor, wherein the cyclin dependentkinase inhibitor is administered as a polypeptide or as a nucleotidesequence that encodes the cyclin dependent kinase inhibitor administeredin an adenoviral viral vector or administered on a sponge depot;

[0445] U.S. Pat. No. 6,455,283, issued Sep. 24, 2002, the entirecontents of which are incorporated herein by reference, discloses amethod of vascular endothelial growth factor-E (VEGF-E). VEGF-E is anovel polypeptide related to vascular endothelial growth factor (VEGF)and bone morphogenetic protein 1. VEGF-E has homology to VEGF includingconservation of the amino acids required for activity of VEGF. VEGF-Ecan be useful in wound repair, as well as in the generation andregeneration of tissue. It is proposed that such VEGF, VEGF-E and theirrespective antagonists with known effects on tissue regeneration oranti-regeneration might be effective in treating trabecular meshwork orocular tissue in general;

[0446] U.S. Pat. No. 6,476,211, issued Nov. 5, 2002, the entire contentsof which are incorporated herein by reference, discloses human CD39-likeprotein polynucleotides isolated from cDNA libraries of human fetalliver-spleen and macrophage as well as polypeptides encoded by thesepolynucleotides and mutants or variants thereof. CD39 (cluster ofdifferentiation 39) is a cell-surface molecule recognized by a “cluster”of monoclonal antibodies that can be used to identify the lineage orstage of differentiation of lymphocytes and thus to distinguish oneclass of lymphocytes from another. It is proposed that such CD39polynucleotides with known effects on antibody specifics might beeffective in treating trabecular meshwork or ocular tissue in general;

[0447] U.S. Pat. No. 5,780,052, issued Jul. 14, 1998, the entirecontents of which are incorporated herein by reference, discloses amethod of salvaging a target cell from cell death, comprising contactinga target cell having a disrupted cell membrane with a specific affinityreagent-liposome conjugate in an amount effective and for a timesufficient to allow the conjugate to prevent cell death due to membranedisruption. The patent discloses methods of delivering a selected agentinto a damaged target cell for diagnosis and therapy, wherein theconjugate comprises a biological agent selected from the groupconsisting of fibroblastic growth factor-β, angiogenic factors, highenergy substrates for the myocardium, antioxidants, cytokines andcontrast agents, which might be effective in treating trabecularmeshwork or ocular tissue in general;

[0448] U.S. Pat. No. 6,475,724, issued Nov. 5, 2002, the entire contentsof which are incorporated herein by reference, discloses a method oftreating glaucoma which comprises administering to a glaucomatouspatient an effective amount of an agent that inhibits the synthesis if aTIGR (trabecular meshwork inducible glucocorticoid response) protein orgene, which might be effective in treating trabecular meshwork or oculartissue in general;

[0449] U.S. Pat. No. 6,475,784, issued Nov. 5, 2002, the entire contentsof which are incorporated herein by reference, discloses a method forpolypeptides having anti-angiogenic activity and nucleic acids thatencode these polypeptides. The anti-angiogenic polypeptides include atleast kringles 1-3 of plasminogen. The patent '784 also provides methodsof using the polypeptides and nucleic acids for inhibiting angiogenesisand other conditions characterized by undesirable endothelial cellproliferation. Angiostatin, which is an angiogenesis inhibitor, is anaturally occurring internal cleavage product of plasminogen, whereinhuman plasminogen has five characteristic protein domains called“kringle structures.” It is proposed that such angiostatin with knowneffects on inhibiting angiogenesis might be effective in treatingtrabecular meshwork and/or ocular tissue in general;

[0450] U.S. Pat. No. 6,436,703, issued Aug. 20, 2002, the entirecontents of which are incorporated herein by reference, discloses amethod and compositions comprising novel isolated polypeptides, novelisolated polynucleotides encoding such polypeptides, includingrecombinant DNA molecules, cloned genes or degenerate variants thereof,especially naturally occurring variants such as allelic variants,antisense polynucleotide molecules, and antibodies that specificallyrecognize one or more epitopes present on such polypeptides, as well ashybridomas producing such antibodies. The compositions in '703additionally include vectors, including expression vectors, containingthe polynucleotides of the invention, cells genetically engineered tocontain such polynucleotides and cells genetically engineered to expresssuch polynucleotides, any of which might be effective in treatingtrabecular meshwork and/or ocular tissue in general;

[0451] U.S. Pat. No. 6,451,764, issued Sep. 17, 2002, the entirecontents of which are incorporated herein by reference, discloses amethod of treating vascular tissue and promoting angiogenesis in amammal comprising administering to the mammal an effective amount of thecomposition comprising VRP (vascular endothelial growth factor-relatedprotein). The disclosure '764 further provides a method for treatingtrauma affecting the vascular endothelium comprising administering to amammal suffering from the trauma an effective amount of the compositioncontaining the VRP, or a method for treating a dysfunctional statecharacterized by lack of activation or lack of inhibition of a receptorfor VRP in a mammal. It is proposed that such angiogenesis promoter andits antagonists with known effects on promoting or inhibitingangiogenesis might be effective in treating trabecular meshwork and/orocular tissue in general; and

[0452] U.S. Pat. No. 5,986,168, issued Nov. 16, 1999, the entirecontents of which are incorporated herein by reference, discloses aprosthesis artificially made in vitro and comprising a time dependentimmobilized and insoluble bioabsorbable substance shaped into aprosthetic shape for implantation into a mammal, and having physicalmeans for immobilizing and insolubilizing of the bioabsorbable substancefor a predetermined period of time after implantation, wherein theprosthesis may comprise fibroblast growth factors, which fibroblastgrowth factors or their antagonists might be effective in treatingtrabecular meshwork and/or ocular tissue in general.

[0453] Scar-Retarding (Antifibrotic) Substances and Background

[0454] It was reported that Monoclonal antibodies are a promisingmodality for prevention of scarring after trabeculectomy, according to acurrent research (OCULAR SURGERY NEWS Sep. 19, 2002 entitled TGF-betamay help prevent postop scarring). Several studies are investigating theinteraction between growth factors and their role in the induction ofpostoperative scarring of the filtering bleb. Wimmer and colleagues notein the September issue of Der Ophthalmologe that among the growthfactors being studied in several trials, TGF-beta 2 plays a keyregulatory function. Its concentration in the aqueous humor of patientswith primary open-angle glaucoma is significantly elevated, and both invivo and in vitro studies have shown the growth factor to demonstrate“promising inhibition of scarring after subconjunctival application.” Inaddition, current research indicates the growth factor is a safe andwell-tolerated approach to managing postop scarring. It is one aspect ofthe present invention to provide a growth factor (TGF-beta 2 and thelike) to trabecular meshwork at an effective amount to mitigate,eliminate, or retard scar formation at or around the trabecularmeshwork. It is a further aspect of the present invention to provide amethod of direct delivery of at least one growth factor (TGF-beta,including TGF-beta 2, analog, derivatives and the like) to trabecularmeshwork at an effective amount to mitigate, eliminate, or retard scarformation at or around the trabecular meshwork to ocular tissue throughan ocularly inserted apparatus or an implant, including a “fistula.” Inone aspect, the bioactive agent of the invention comprises a scarretarding substance.

[0455] U.S. Pat. No. 5,324,508, issued Jun. 28, 1994, the entirecontents of which are incorporated herein by reference, discloses amacrophage monokine product having a molecular weight of no more thanabout 10,000 Dalton, wherein the macrophage monokine appears to begenerally effective in inhibiting scar tissue. It is one object of thepresent invention to incorporate the macrophage monokine product onto atrabecular stent for scar management.

[0456] Prof. Peng Khaw (of the Institute of Ophthalmology and MoorfieldsEye Hospital) discloses that injecting a neutralizing antibody to theprotein transforming growth factor beta₂ (TGF-b₂) after glaucoma surgeryreduced the scarring that is the primary cause for poor postoperativeIOP control in a pilot clinical study conducted at Moorfields EyeHospital and the Western Eye Hospital. Scarring after surgery is themain cause of treatment failures, but the attempt to diminish scarringwith anti-cancer drugs can lead to its own set of problems.

[0457] Anti-cancer drugs used with glaucoma surgery, which to date haveincluded 5-fluorouracil (5FU) and mitomycin-C, can lead to the creationof acellular, thin, cystic drainage blebs that may leak, resulting inhypotony and potentially blinding infections. Anti-cancer drugs work bykilling cells, so they have a lot of potential side effects. Therefore,they are not the ideal treatment, particularly if you want to optimizethe pressure lowering in every patient having surgery.

[0458] Scarring processes are a big problem in the eye and surroundingstructures. Scarring plays a part in either the primary disease ortreatment failure of most blinding conditions in the world today. Anexception to this repair response is found in the fetal stage, whenscarring is minimal. Instead, regeneration primarily occurs. This isassociated with low levels of TGF-b in the womb.

[0459] It is therefore one aspect of the present invention to provide amethod of maintaining a fistula in trabecular meshwork with ascar-retarding substance for re-establishing physiologic outflow in theeye. In one embodiment, the fistula is biodegradable.

[0460] U.S. Pat. No. 5,922,369, entire contents of which areincorporated herein by reference, discloses a method of treating eyeconditions with human leukocyte elastase (HLE) inhibitory agents. Morespecifically, it is one object of the present invention to provide amethod of reducing tissue or corneal scarring comprising delivery ofhuman leukocyte elastase inhibitory agents an effective amount for scarreducing of a free or polymer-bound HLE inhibitory agent to oculartissue through an ocularly inserted apparatus or an implant, including afistula.

[0461]FIG. 65 shows one embodiment for a fistula without a lumen fortransporting aqueous. The fistula may be made of a soft flexiblematerial with special surface characteristics to facilitate aqueoustransporting along its surface. The material may be selected from agroup consisting of silicone, polyurethane, acrylics, and the like. Thespecial surface characteristics for facilitating aqueous transportationmay include hydrophilicity, hydrophobicity, surface charge, heparinizedsurface, surface pH, and drug-coated surface. The surfacecharacteristics may also include mechanical or physical properties suchas surface elasticity, surface configuration, shape memory and the like.FIG. 65 shows a fistula 466 comprising a proximal terminal means 467sized and shaped to be received within the anterior chamber 20 and adistal terminal means 468 sized and shaped to be received withinSchlemm's canal 22. A majority of the surface 469 with specialcharacteristics contacts the trabecular meshwork 21 where thefacilitated aqueous transportation takes places. The cross-sectionalconfiguration may be any shape, including circular, oval, star, random,and arbitrary or the like.

[0462] Some aspects of the invention provides a trabecular bypass stentthat is implantable within an eye, the device comprising: an inletsection having an inlet end exposed to an anterior chamber; an outletsection having an outlet end exposed to Schlemm's canal, wherein thedevice is configured to permit fluid entering the inlet end and thenexiting the outlet end; and at least one bioactive agent is loaded ontothe stent, wherein the bioactive agent is selected from a groupconsisting of TGF-beta, a gene, a growth factor, a scar-retarding (orscar-mitigating, scar-limiting, scar-inhibiting) substance. In oneaspect of the invention, the therapy combines at least one bioactiveagent loaded onto a trabecular bypass stent and a topically administeredIOP-lowering eye drop medicine selected from a group consisting (1)Miotics (e.g., pilocarpine, carbachol, and acetylcholinesteraseinhibitors), (2) Sympathomimetics (e.g., epinephrine anddipivalylepinephxine), (3) Beta-blockers (e.g., betaxolol, levobunololand timolol), (4) Carbonic anhydrase inhibitors (e.g., acetazolamide,methazolamide and ethoxzolamide), and (5) Prostaglandins (e.g.,metabolite derivatives of arachindonic acid).

[0463] Although preferred embodiments of the invention have beendescribed in detail, including devices loaded with TGF-beta and/orbioactive agents, certain variations and modifications will be apparentto those skilled in the art, including embodiments that do not provideall of the features and benefits described herein. Accordingly, thescope of the present invention is not to be limited by the illustrationsor the foregoing descriptions thereof, but rather solely by reference tothe appended claims and their equivalents.

What is claimed is:
 1. An implant for treating glaucoma, comprising: abody comprising material that includes a drug, said body having an inletportion and an outlet portion, said inlet portion configured totransport fluid from the anterior chamber of an eye to the outletportion when the outlet portion is disposed in Schlemm's canal of theeye, said outlet portion having an outflow opening.
 2. The implant ofclaim 1, wherein said body is coated with said drug.
 3. The implant ofclaim 1, wherein said drug comprises heparin.
 4. An implant for treatingglaucoma, comprising: a body having a bioactive agent in or on saidbody, said body having an inlet portion and an outlet portion, saidinlet portion configured to transmit fluid from the anterior chamber tothe outlet portion when the outlet portion is disposed in Schlemm'scanal, said outlet portion having an outflow opening.
 5. The implant ofclaim 4, wherein said body is coated with said bioactive agent.
 6. Theimplant of claim 4, wherein said bioactive agent comprises heparin. 7.The implant of claim 4, wherein said bioactive agent comprises TGF-beta.8. The implant of claim 4, wherein said bioactive agent comprises agene.
 9. The implant of claim 4, wherein said bioactive agent comprisesan anti-inflammatory drug.
 10. The implant of claim 4, wherein saidbioactive agent comprises an intraocular pressure-lowering drug.
 11. Theimplant of claim 4, wherein said bioactive agent comprises a growthfactor.
 12. The implant of claim 4, wherein said bioactive agentcomprises an antiproliferative agent.
 13. The implant of claim 4,wherein said bioactive agent is loaded onto a surface of the outletsection.
 14. The implant of claim 4, further comprising a biodegradablematerial in or on said implant.
 15. The implant of claim 14, wherein thebiodegradable material is selected from the group consisting ofpoly(lactic acid), polyethylene-vinyl acetate, poly(lactic-co-glycolicacid), poly(D,L-lactide), poly(D,L-lactide-co-trimethylene carbonate),collagen, heparinized collagen, poly(caprolactone), poly(glycolic acid),and a copolymer.
 16. The implant of claim 4, wherein the outlet endfurther comprises a plurality of pillars at said outlet end.
 17. Thedevice of claim 16, wherein the bioactive agent is in or on at least oneof said pillars.
 18. The implant of claim 4, wherein said implant is atleast partially coated with at least one polymer film that contains thebioactive agent, said polymer film permitting a delivery of a quantityof the bioactive agent to ocular tissues over time.
 19. An ocularimplant comprising: a body having a bioactive agent in or on said body,said body further comprising: an inlet section configured to bepositioned in the anterior chamber of an eye; an outlet sectionconfigured to be positioned at least partially in Schlemm's canal ofsaid eye, said outlet section being in fluid communication with saidinlet section; a lumen extending between said inlet section and saidoutlet section; and a flow-restricting member within the lumen, saidflow-restricting member being configured to prevent at least onecomponent of blood from passing through the flow-restricting member. 20.The implant of claim 19, wherein said body is coated with said bioactiveagent.
 21. The implant of claim 19, wherein said bioactive agentcomprises heparin.
 22. The implant of claim 19, wherein said bioactiveagent comprises TGF-beta.
 23. The implant of claim 19, wherein saidbioactive agent comprises a gene.
 24. The implant of claim 19, whereinsaid bioactive agent comprises an anti-inflammatory drug.
 25. Theimplant of claim 19, wherein said bioactive agent comprises anintraocular pressure-lowering drug.
 26. The implant of claim 19, whereinsaid bioactive agent comprises a growth factor.
 27. The implant of claim19, wherein said bioactive agent comprises an antiproliferative agent.28. The implant of claim 19, wherein said bioactive agent is loaded ontoa surface of the outlet section.
 29. The implant of claim 19, furthercomprising a biodegradable material in or on said implant.
 30. Theimplant of claim 29, wherein the biodegradable material is selected fromthe group consisting of poly(lactic acid), polyethylene-vinyl acetate,poly(lactic-co-glycolic acid), poly(D,L-lactide),poly(D,L-lactide-co-trimethylene carbonate), collagen, heparinizedcollagen, poly(caprolactone), poly(glycolic acid), and a copolymer. 31.The implant of claim 19, wherein said bioactive agent comprises anImidazole antiproliferative agent.
 32. The implant of claim 19, whereinsaid bioactive agent comprises a quinoxaline.
 33. The implant of claim19, wherein said bioactive agent comprises a phsophonylmethoxyalkylnucleotide analog.
 34. The implant of claim 19, wherein said bioactiveagent comprises a potassium channel blocker.
 35. The implant of claim19, wherein said bioactive agent comprises a synthetic oligonucleotide.36. The implant of claim 19, wherein said bioactive agent comprises5-[1-hydroxy-2-[2-(2-methoxyphenoxyl)ethylamino]ethyl]-2-methylbenzenesulfonamide.37. The implant of claim 19, wherein said bioactive agent comprises aguanylate cyclase inhibitor.
 38. The method of claim 37, wherein theguanylate cyclase inhibitor in selected from the group consisting ofmethylene blue, butylated hydroxyanisole, and N-methylhydroxylamine. 39.The implant of claim 19, wherein said bioactive agent comprises2-(4-methylaminobutoxy) diphenylmethane.
 40. The implant of claim 19,wherein said bioactive agent comprises a combination of apraclonidineand timolol.
 41. The implant of claim 19, wherein said bioactive agentcomprises a cloprostenol analog or a fluprostenol analog.
 42. Theimplant of claim 19, wherein said bioactive agent comprises acrosslinked carboxy-containing polymer, a sugar, and water.
 43. Theimplant of claim 19, wherein said bioactive agent comprises anon-corneotoxic serine-threonine kinase inhibitor.
 44. The implant ofclaim 19, wherein said bioactive agent comprises a nonsteroidalglucocorticoid antagonist.
 45. The implant of claim 19, wherein saidbioactive agent comprises a prostaglandin analog or a derivativethereof.